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Sample records for therapy response prediction

  1. Predicting response to epigenetic therapy

    DEFF Research Database (Denmark)

    Treppendahl, Marianne B; Sommer Kristensen, Lasse; Grønbæk, Kirsten

    2014-01-01

    of good pretreatment predictors of response is of great value. Many clinical parameters and molecular targets have been tested in preclinical and clinical studies with varying results, leaving room for optimization. Here we provide an overview of markers that may predict the efficacy of FDA- and EMA...

  2. Pre-treatment amygdala volume predicts electroconvulsive therapy response

    NARCIS (Netherlands)

    ten Doesschate, Freek; van Eijndhoven, Philip; Tendolkar, Indira; van Wingen, Guido A.; van Waarde, Jeroen A.

    2014-01-01

    Electroconvulsive therapy (ECT) is an effective treatment for patients with severe depression. Knowledge on factors predicting therapeutic response may help to identify patients who will benefit most from the intervention. Based on the neuroplasticity hypothesis, volumes of the amygdala and

  3. Predicting response to antimicrobial therapy in children with acute sinusitis

    Science.gov (United States)

    Shaikh, Nader; Wald, Ellen R.; Jeong, Jong H.; Kurs-Lasky, Marcia; Bowen, A’Delbert; Flom, Lynda L.; Hoberman, Alejandro

    2014-01-01

    Objective To determine prognostic factors that independently predict response to antimicrobial therapy in children with acute sinusitis. Study design 206 children meeting a priori clinical criteria for acute sinusitis who were given antimicrobial therapy by their primary care provider were included. The severity of symptoms in the 8 to 12 days after treatment was initiated was followed using a validated scale. We examined the univariate and multivariate association between factors present at the time of diagnosis (symptoms, signs, nasopharyngeal culture result, radiograph results) and time to resolution of symptoms. This study was conducted 8 to 10 years after 7-valent pneumococcal conjugate vaccination was introduced, but before introduction of the 13-valent pneumococcal conjugate vaccination. Results Children with proven nasopharyngeal colonization with Streptococcus pneumoniae improved more rapidly (6.5 vs. 8.5 median days to symptom resolution) than those who were not colonized with S. pneumoniae. Age and radiograph findings did not predict time to symptom resolution. Conclusions In children with acute sinusitis, proven nasopharyngeal colonization with S. pneumoniae at presentation independently predicted time to symptom resolution. Future randomized, placebo-controlled trials could investigate the usefulness of testing for the presence of nasopharyngeal pathogens as a predictor of response to treatment. PMID:24367985

  4. Predicting response to antimicrobial therapy in children with acute sinusitis.

    Science.gov (United States)

    Shaikh, Nader; Wald, Ellen R; Jeong, Jong H; Kurs-Lasky, Marcia; Bowen, A'delbert; Flom, Lynda L; Hoberman, Alejandro

    2014-03-01

    To determine prognostic factors that independently predict response to antimicrobial therapy in children with acute sinusitis. A total of 206 children meeting a priori clinical criteria for acute sinusitis who were prescribed antimicrobial therapy by their primary care provider were included. The severity of symptoms in the 8-12 days after treatment was initiated was followed with the use of a validated scale. We examined the univariate and multivariate association between factors present at the time of diagnosis (symptoms, signs, nasopharyngeal culture result, radiograph results) and time to resolution of symptoms. This study was conducted 8-10 years after the 7-valent pneumococcal conjugate vaccination was introduced but before introduction of the 13-valent pneumococcal conjugate vaccination. Children with proven nasopharyngeal colonization with Streptococcus pneumoniae improved more rapidly (6.5 vs 8.5 median days to symptom resolution) than those who were not colonized with S pneumoniae. Age and radiograph findings did not predict time to symptom resolution. In children with acute sinusitis, proven nasopharyngeal colonization with S pneumoniae at presentation independently predicted time to symptom resolution. Future randomized, placebo-controlled trials could investigate the usefulness of testing for the presence of nasopharyngeal pathogens as a predictor of response to treatment. Copyright © 2014 Mosby, Inc. All rights reserved.

  5. Data to establish the optimal standard regimen and predicting the response to docetaxel therapy

    Directory of Open Access Journals (Sweden)

    Emad Y. Moawad

    2015-12-01

    Full Text Available This paper contains data to establish the optimal standard regimen and predicting the response to docetaxel therapy (Moawad, 2014 [1]. Docetaxel has been in use for over a decade without demonstrating data indicates a predictable response in the treatment of cancer. Data of puzzling response to docetaxel therapy was due to its cell cycle specific effect. Although several administered schedules were investigated, the relative therapeutic advantage of high versus low doses has not been identified yet. Also the antitumor target of docetaxel has not yet been identified to optimize therapy by predicting the response of patients prior to therapy to provide a protection against treatment failure. In the present paper, we demonstrate the data used to optimize docetaxel therapy and investigate the possibility of predicting for the first time the antitumor target of docetaxel.

  6. Can Nutritional Assessment Tools Predict Response to Nutritional Therapy?

    Science.gov (United States)

    Patel, Chirag; Omer, Endashaw; Diamond, Sarah J; McClave, Stephen A

    2016-04-01

    Traditional tools and scoring systems for nutritional assessment have focused solely on parameters of poor nutritional status in the past, in an effort to define the elusive concept of malnutrition. Such tools fail to account for the contribution of disease severity to overall nutritional risk. High nutritional risk, caused by either deterioration of nutritional status or greater disease severity (or a combination of both factors), puts the patient in a metabolic stress state characterized by adverse outcome and increased complications. Newer scoring systems for determining nutritional risk, such as the Nutric Score and the Nutritional Risk Score-2002 have created a paradigm shift connecting assessment and treatment with quality outcome measures of success. Clinicians now have the opportunity to identify high risk patients through their initial assessment, provide adequate or sufficient nutrition therapy, and expect improved patient outcomes as a result. These concepts are supported by observational and prospective interventional trials. Greater clinical experience and refinement in these scoring systems are needed in the future to optimize patient response to nutrition therapy.

  7. Distinct Functional Connectivities Predict Clinical Response with Emotion Regulation Therapy

    National Research Council Canada - National Science Library

    Liston, Conor; Roy, Amy K; Fresco, David M; Adelsberg, Samantha; Mennin, Douglas S; Garcia-Lesy, Emmanuel; Seeley, Saren

    2017-01-01

    ... associated with emotional/motivational salience (e.g., salience network) and self-referentiality (e.g., default network). Emotion Regulation Therapy (ERT) was developed to target this hypothesi...

  8. Use of molecular markers for predicting therapy response in cancer patients.

    LENUS (Irish Health Repository)

    Duffy, Michael J

    2012-02-01

    Predictive markers are factors that are associated with upfront response or resistance to a particular therapy. Predictive markers are important in oncology as tumors of the same tissue of origin vary widely in their response to most available systemic therapies. Currently recommended oncological predictive markers include both estrogen and progesterone receptors for identifying patients with breast cancers likely to benefit from hormone therapy, HER-2 for the identification of breast cancer patients likely to benefit from trastuzumab, specific K-RAS mutations for the identification of patients with advanced colorectal cancer unlikely to benefit from either cetuximab or panitumumab and specific EGFR mutations for selecting patients with advanced non-small-cell lung cancer for treatment with tyrosine kinase inhibitors such as gefitinib and erlotinib. The availability of predictive markers should increase drug efficacy and decrease toxicity, thus leading to a more personalized approach to cancer treatment.

  9. Sleep spindles may predict response to cognitive-behavioral therapy for chronic insomnia.

    Science.gov (United States)

    Dang-Vu, Thien Thanh; Hatch, Benjamin; Salimi, Ali; Mograss, Melodee; Boucetta, Soufiane; O'Byrne, Jordan; Brandewinder, Marie; Berthomier, Christian; Gouin, Jean-Philippe

    2017-11-01

    While cognitive-behavioral therapy for insomnia constitutes the first-line treatment for chronic insomnia, only few reports have investigated how sleep architecture relates to response to this treatment. In this pilot study, we aimed to determine whether pre-treatment sleep spindle density predicts treatment response to cognitive-behavioral therapy for insomnia. Twenty-four participants with chronic primary insomnia participated in a 6-week cognitive-behavioral therapy for insomnia performed in groups of 4-6 participants. Treatment response was assessed using the Pittsburgh Sleep Quality Index and the Insomnia Severity Index measured at pre- and post-treatment, and at 3- and 12-months' follow-up assessments. Secondary outcome measures were extracted from sleep diaries over 7 days and overnight polysomnography, obtained at pre- and post-treatment. Spindle density during stage N2-N3 sleep was extracted from polysomnography at pre-treatment. Hierarchical linear modeling analysis assessed whether sleep spindle density predicted response to cognitive-behavioral therapy. After adjusting for age, sex, and education level, lower spindle density at pre-treatment predicted poorer response over the 12-month follow-up, as reflected by a smaller reduction in Pittsburgh Sleep Quality Index over time. Reduced spindle density also predicted lower improvements in sleep diary sleep efficiency and wake after sleep onset immediately after treatment. There were no significant associations between spindle density and changes in the Insomnia Severity Index or polysomnography variables over time. These preliminary results suggest that inter-individual differences in sleep spindle density in insomnia may represent an endogenous biomarker predicting responsiveness to cognitive-behavioral therapy. Insomnia with altered spindle activity might constitute an insomnia subtype characterized by a neurophysiological vulnerability to sleep disruption associated with impaired responsiveness to

  10. Prediction of response to interferon therapy in multiple sclerosis

    DEFF Research Database (Denmark)

    Sellebjerg, F; Søndergaard, Helle Bach; Koch-Henriksen, N

    2014-01-01

    OBJECTIVE: Single nucleotide polymorphisms (SNPs) in the genes encoding interferon response factor (IRF)-5, IRF-8 and glypican-5 (GPC5) have been associated with disease activity in multiple sclerosis (MS) patients treated with interferon (IFN)-β. We analysed whether SNPs in the IRF5, IRF8 and GPC5...... prospectively after the initiation of their first treatment with IFN-β. RESULTS: 62% of patients experienced relapses during the first 2 years of treatment, and 32% had disability progression during the first 5 years of treatment. Patients with a pretreatment annualized relapse rate >1 had an increased risk...

  11. Towards personalized therapy for multiple sclerosis: prediction of individual treatment response.

    Science.gov (United States)

    Kalincik, Tomas; Manouchehrinia, Ali; Sobisek, Lukas; Jokubaitis, Vilija; Spelman, Tim; Horakova, Dana; Havrdova, Eva; Trojano, Maria; Izquierdo, Guillermo; Lugaresi, Alessandra; Girard, Marc; Prat, Alexandre; Duquette, Pierre; Grammond, Pierre; Sola, Patrizia; Hupperts, Raymond; Grand'Maison, Francois; Pucci, Eugenio; Boz, Cavit; Alroughani, Raed; Van Pesch, Vincent; Lechner-Scott, Jeannette; Terzi, Murat; Bergamaschi, Roberto; Iuliano, Gerardo; Granella, Franco; Spitaleri, Daniele; Shaygannejad, Vahid; Oreja-Guevara, Celia; Slee, Mark; Ampapa, Radek; Verheul, Freek; McCombe, Pamela; Olascoaga, Javier; Amato, Maria Pia; Vucic, Steve; Hodgkinson, Suzanne; Ramo-Tello, Cristina; Flechter, Shlomo; Cristiano, Edgardo; Rozsa, Csilla; Moore, Fraser; Luis Sanchez-Menoyo, Jose; Laura Saladino, Maria; Barnett, Michael; Hillert, Jan; Butzkueven, Helmut

    2017-09-01

    Timely initiation of effective therapy is crucial for preventing disability in multiple sclerosis; however, treatment response varies greatly among patients. Comprehensive predictive models of individual treatment response are lacking. Our aims were: (i) to develop predictive algorithms for individual treatment response using demographic, clinical and paraclinical predictors in patients with multiple sclerosis; and (ii) to evaluate accuracy, and internal and external validity of these algorithms. This study evaluated 27 demographic, clinical and paraclinical predictors of individual response to seven disease-modifying therapies in MSBase, a large global cohort study. Treatment response was analysed separately for disability progression, disability regression, relapse frequency, conversion to secondary progressive disease, change in the cumulative disease burden, and the probability of treatment discontinuation. Multivariable survival and generalized linear models were used, together with the principal component analysis to reduce model dimensionality and prevent overparameterization. Accuracy of the individual prediction was tested and its internal validity was evaluated in a separate, non-overlapping cohort. External validity was evaluated in a geographically distinct cohort, the Swedish Multiple Sclerosis Registry. In the training cohort (n = 8513), the most prominent modifiers of treatment response comprised age, disease duration, disease course, previous relapse activity, disability, predominant relapse phenotype and previous therapy. Importantly, the magnitude and direction of the associations varied among therapies and disease outcomes. Higher probability of disability progression during treatment with injectable therapies was predominantly associated with a greater disability at treatment start and the previous therapy. For fingolimod, natalizumab or mitoxantrone, it was mainly associated with lower pretreatment relapse activity. The probability of

  12. Challenges in defining predictive markers for response to endocrine therapy in breast cancer.

    Science.gov (United States)

    Larionov, Alexey A; Miller, William R

    2009-11-01

    Endocrine therapy is a major treatment modality for hormone-dependent breast cancer. It has a relatively low morbidity, and there is evidence that antihormonal treatments have had a significant effect in reducing mortality for breast cancer. Despite this, resistance to endocrine therapy, either primary or acquired during treatment, occurs in the majority of patients, and is a major obstacle to optimal clinical management. There is therefore an urgent need to identify, on an individual basis, those tumors that are most likely to respond to endocrine therapy (so sparing patients with resistant tumors the needless side effects of ineffective therapy), and the mechanisms of resistance in tumors that are nonresponsive to treatment (so these can be bypassed). These needs are the focus of this review, which discusses the particular issues encountered when investigating the potential of multigene expression signatures as predictive factors for response to aromatase inhibitors, which have recently become front-line endocrine therapies for postmenopausal patients with breast cancer.

  13. Psychic and somatic anxiety differentially predict response to light therapy in women with seasonal affective disorder.

    Science.gov (United States)

    MacKenzie, Bronwyn; Levitan, Robert D

    2005-10-01

    To examine whether psychic and/or somatic anxiety predict responsiveness to light therapy in women with winter Seasonal Affective Disorder (SAD). Eighty-one women with SAD were administered a standard 10-day trial of light therapy administered for one-half hour in the early morning. Using a multiple regression model, baseline somatic and psychic anxiety item scores were used to predict percentage change scores on the 29-item SIGH-SAD post treatment. Baseline scores for weight gain, hypersomnia and the total SIGH-SAD were also included as predictor variables. The regression model was highly significant (F=4.63, df=5,75; p=.001; model R(2)=.236), with both psychic anxiety and somatic anxiety contributing significantly to the model. Consistent with prior work using anti-depressant medication in non-seasonal depression, psychic anxiety was positively correlated with outcome, while somatic anxiety negatively predicted outcome. In SAD, psychic and somatic anxiety scores at baseline appear to be independent and opposite predictors of light therapy response. These effects were independent of baseline scores for weight gain and hypersomnia, two previously established predictors of response to light. These findings may be an important consideration in the design and interpretation of light therapy studies of SAD.

  14. Elevation in inflammatory serum biomarkers predicts response to trastuzumab-containing therapy.

    Directory of Open Access Journals (Sweden)

    Ahmed A Alkhateeb

    Full Text Available Approximately half of all HER2/neu-overexpressing breast cancer patients do not respond to trastuzumab-containing therapy. Therefore, there remains an urgent and unmet clinical need for the development of predictive biomarkers for trastuzumab response. Recently, several lines of evidence have demonstrated that the inflammatory tumor microenvironment is a major contributor to therapy resistance in breast cancer. In order to explore the predictive value of inflammation in breast cancer patients, we measured the inflammatory biomarkers serum ferritin and C-reactive protein (CRP in 66 patients immediately before undergoing trastuzumab-containing therapy and evaluated their progression-free and overall survival. The elevation in pre-treatment serum ferritin (>250 ng/ml or CRP (>7.25 mg/l was a significant predictor of reduced progression-free survival and shorter overall survival. When patients were stratified based on their serum ferritin and CRP levels, patients with elevation in both inflammatory biomarkers had a markedly poorer response to trastuzumab-containing therapy. Therefore, the elevation in inflammatory serum biomarkers may reflect a pathological state that decreases the clinical efficacy of this therapy. Anti-inflammatory drugs and life-style changes to decrease inflammation in cancer patients should be explored as possible strategies to sensitize patients to anti-cancer therapeutics.

  15. Therapygenetics: 5-HTTLPR genotype predicts the response to exposure therapy for agoraphobia.

    Science.gov (United States)

    Knuts, Inge; Esquivel, Gabriel; Kenis, Gunter; Overbeek, Thea; Leibold, Nicole; Goossens, Lies; Schruers, Koen

    2014-08-01

    This study was intended to assess the extent to which the low-expression allele of the serotonin transporter gene promoter predicts better response to exposure-based behavior therapy in patients with panic disorder with agoraphobia (PDA). Ninety-nine patients with PDA underwent a 1-week in vivo exposure-based behavior therapy program and provided saliva samples to extract genomic DNA and classify individuals according to four allelic forms (SA, SG, LA, LG) of the 5-HTT-linked polymorphic region (5-HTTLPR). We determined whether the 5-HTTLPR genotype predicted change in avoidance behavior in PDA following treatment. After controlling for pre-treatment avoidance behavior, the 5-HTTLPR low-expression genotypes showed a more favorable response to exposure therapy two weeks following treatment, compared to the other patients. This study suggests a genetic contribution to treatment outcome following behavior therapy and implicates the serotonergic system in response to exposure-based treatments in PDA. Copyright © 2014 Elsevier B.V. and ECNP. All rights reserved.

  16. Anterior cingulate volume predicts response to cognitive behavioral therapy in major depressive disorder.

    Science.gov (United States)

    Fujino, Junya; Yamasaki, Nobuyuki; Miyata, Jun; Sasaki, Hitoshi; Matsukawa, Noriko; Takemura, Ariyoshi; Tei, Shisei; Sugihara, Genichi; Aso, Toshihiko; Fukuyama, Hidenao; Takahashi, Hidehiko; Inoue, Kazuomi; Murai, Toshiya

    2015-03-15

    Cognitive behavioral therapy (CBT) is widely used to treat major depressive disorder (MDD). Although improved response prediction could facilitate the development of individualized treatment plans, few studies have investigated whether underlying brain structure is related to CBT response in MDD. Ten MDD patients who received individual CBT were studied in this study. We investigated the relationship between the regional gray matter (GM) volume and subsequent responses to CBT using voxel-based morphometry. The degree of improvement in depressive symptoms was positively correlated with GM volume in the caudal portion of the anterior cingulate cortex. The sample size was small, and the effects of medication on the results could not be excluded. Our results, although preliminary, suggest that the anterior cingulate cortex is a key structure whose volume can be used to predict responses to CBT and is thus a potential prognostic marker in MDD. Copyright © 2014 Elsevier B.V. All rights reserved.

  17. Alkaline phosphatase predicts response in polycystic liver disease during somatostatin analogue therapy: a pooled analysis.

    Science.gov (United States)

    Gevers, Tom J G; Nevens, Frederik; Torres, Vicente E; Hogan, Marie C; Drenth, Joost P H

    2016-04-01

    Somatostatin analogues reduce liver volumes in polycystic liver disease. However, patients show considerable variability in treatment responses. Our aim was to identify specific patient, disease or treatment characteristics that predict response in polycystic liver disease during somatostatin analogue therapy. We pooled the individual patient data of four trials that evaluated long-acting somatostatin analogues (120 mg lanreotide or 40 mg octreotide) for 6-12 months in polycystic liver disease patients. We performed uni- and multivariate linear regression analysis with preselected patient, disease and drug variables to identify independent predictors of response, defined as per cent change in liver or kidney volume (in ADPKD subgroup). All analyses were adjusted for baseline liver volume and centre. We included 153 polycystic liver disease patients (86% female, median liver volume 4974 ml) from three international centres, all treated with octreotide (n = 70) or lanreotide (n = 83). Mean reduction in liver volume was 4.4% (range -31.6 to +9.4%). Multivariate linear regression revealed that elevated baseline alkaline phosphatase was associated with increased liver volume reduction during therapy (-2.7%, 95% CI -5.1 to -0.2%, P = 0.04), independently of baseline liver volume. Somatostatin analogue type, underlying diagnosis and eGFR did not affect response. In our ADPKD subpopulation (n = 100), elevated alkaline phosphatase predicted liver volume reduction (-3.2%, P = 0.03) but did not predict kidney volume reduction (+0.1%, P = 0.97). Total gastro-intestinal symptom severity decreased with therapy in a subgroup analysis (n = 95; P Alkaline phosphatase is a liver-specific, independent predictor of response in polycystic liver disease during somatostatin analogue therapy. © 2015 John Wiley & Sons A/S. Published by John Wiley & Sons Ltd.

  18. Accurate Prediction and Validation of Response to Endocrine Therapy in Breast Cancer.

    Science.gov (United States)

    Turnbull, Arran K; Arthur, Laura M; Renshaw, Lorna; Larionov, Alexey A; Kay, Charlene; Dunbier, Anita K; Thomas, Jeremy S; Dowsett, Mitch; Sims, Andrew H; Dixon, J Michael

    2015-07-10

    Aromatase inhibitors (AIs) have an established role in the treatment of breast cancer. Response rates are only 50% to 70% in the neoadjuvant setting and lower in advanced disease. Accurate biomarkers are urgently needed to predict response in these settings and to determine which individuals will benefit from adjuvant AI therapy. Pretreatment and on-treatment (after 2 weeks and 3 months) biopsies were obtained from 89 postmenopausal women who had estrogen receptor-alpha positive breast cancer and were receiving neoadjuvant letrozole for transcript profiling. Dynamic clinical response was assessed with use of three-dimensional ultrasound measurements. The molecular response to letrozole was characterized and a four-gene classifier of clinical response was established (accuracy of 96%) on the basis of the level of two genes before treatment (one gene [IL6ST] was associated with immune signaling, and the other [NGFRAP1] was associated with apoptosis) and the level of two proliferation genes (ASPM, MCM4) after 2 weeks of therapy. The four-gene signature was found to be 91% accurate in a blinded, completely independent validation data set of patients treated with anastrozole. Matched 2-week on-treatment biopsies were associated with improved predictive power as compared with pretreatment biopsies alone. This signature also significantly predicted recurrence-free survival (P = .029) and breast cancer -specific survival (P = .009). We demonstrate that the test can also be performed with use of quantitative polymerase chain reaction or immunohistochemistry. A four-gene predictive model of clinical response to AIs by 2 weeks has been generated and validated. Deregulated immune and apoptotic responses before treatment and cell proliferation that is not reduced 2 weeks after initiation of treatment are functional characteristics of breast tumors that do not respond to AIs. © 2015 by American Society of Clinical Oncology.

  19. Prediction of Individual Response to Electroconvulsive Therapy via Machine Learning on Structural Magnetic Resonance Imaging Data.

    Science.gov (United States)

    Redlich, Ronny; Opel, Nils; Grotegerd, Dominik; Dohm, Katharina; Zaremba, Dario; Bürger, Christian; Münker, Sandra; Mühlmann, Lisa; Wahl, Patricia; Heindel, Walter; Arolt, Volker; Alferink, Judith; Zwanzger, Peter; Zavorotnyy, Maxim; Kugel, Harald; Dannlowski, Udo

    2016-06-01

    Electroconvulsive therapy (ECT) is one of the most effective treatments for severe depression. However, biomarkers that accurately predict a response to ECT remain unidentified. To investigate whether certain factors identified by structural magnetic resonance imaging (MRI) techniques are able to predict ECT response. In this nonrandomized prospective study, gray matter structure was assessed twice at approximately 6 weeks apart using 3-T MRI and voxel-based morphometry. Patients were recruited through the inpatient service of the Department of Psychiatry, University of Muenster, from March 11, 2010, to March 27, 2015. Two patient groups with acute major depressive disorder were included. One group received an ECT series in addition to antidepressants (n = 24); a comparison sample was treated solely with antidepressants (n = 23). Both groups were compared with a sample of healthy control participants (n = 21). Binary pattern classification was used to predict ECT response by structural MRI that was performed before treatment. In addition, univariate analysis was conducted to predict reduction of the Hamilton Depression Rating Scale score by pretreatment gray matter volumes and to investigate ECT-related structural changes. One participant in the ECT sample was excluded from the analysis, leaving 67 participants (27 men and 40 women; mean [SD] age, 43.7 [10.6] years). The binary pattern classification yielded a successful prediction of ECT response, with accuracy rates of 78.3% (18 of 23 patients in the ECT sample) and sensitivity rates of 100% (13 of 13 who responded to ECT). Furthermore, a support vector regression yielded a significant prediction of relative reduction in the Hamilton Depression Rating Scale score. The principal findings of the univariate model indicated a positive association between pretreatment subgenual cingulate volume and individual ECT response (Montreal Neurological Institute [MNI] coordinates x = 8, y = 21, z = -18

  20. Molecular Biomarkers for Prediction of Targeted Therapy Response in Metastatic Breast Cancer: Trick or Treat?

    Science.gov (United States)

    Toss, Angela; Venturelli, Marta; Peterle, Chiara; Piacentini, Federico; Cascinu, Stefano; Cortesi, Laura

    2017-01-04

    In recent years, the study of genomic alterations and protein expression involved in the pathways of breast cancer carcinogenesis has provided an increasing number of targets for drugs development in the setting of metastatic breast cancer (i.e., trastuzumab, everolimus, palbociclib, etc.) significantly improving the prognosis of this disease. These drugs target specific molecular abnormalities that confer a survival advantage to cancer cells. On these bases, emerging evidence from clinical trials provided increasing proof that the genetic landscape of any tumor may dictate its sensitivity or resistance profile to specific agents and some studies have already showed that tumors treated with therapies matched with their molecular alterations obtain higher objective response rates and longer survival. Predictive molecular biomarkers may optimize the selection of effective therapies, thus reducing treatment costs and side effects. This review offers an overview of the main molecular pathways involved in breast carcinogenesis, the targeted therapies developed to inhibit these pathways, the principal mechanisms of resistance and, finally, the molecular biomarkers that, to date, are demonstrated in clinical trials to predict response/resistance to targeted treatments in metastatic breast cancer.

  1. Molecular Biomarkers for Prediction of Targeted Therapy Response in Metastatic Breast Cancer: Trick or Treat?

    Directory of Open Access Journals (Sweden)

    Angela Toss

    2017-01-01

    Full Text Available In recent years, the study of genomic alterations and protein expression involved in the pathways of breast cancer carcinogenesis has provided an increasing number of targets for drugs development in the setting of metastatic breast cancer (i.e., trastuzumab, everolimus, palbociclib, etc. significantly improving the prognosis of this disease. These drugs target specific molecular abnormalities that confer a survival advantage to cancer cells. On these bases, emerging evidence from clinical trials provided increasing proof that the genetic landscape of any tumor may dictate its sensitivity or resistance profile to specific agents and some studies have already showed that tumors treated with therapies matched with their molecular alterations obtain higher objective response rates and longer survival. Predictive molecular biomarkers may optimize the selection of effective therapies, thus reducing treatment costs and side effects. This review offers an overview of the main molecular pathways involved in breast carcinogenesis, the targeted therapies developed to inhibit these pathways, the principal mechanisms of resistance and, finally, the molecular biomarkers that, to date, are demonstrated in clinical trials to predict response/resistance to targeted treatments in metastatic breast cancer.

  2. Elevated Serum Interleukin-6 Predicts Favorable Response to Immunosuppressive Therapy in Children With Aplastic Anemia.

    Science.gov (United States)

    Lu, Shuanglong; Qiao, Xiaohong; Xie, Xiaotian

    2017-11-01

    Immunosuppressive therapy (IST) is the standard treatment for aplastic anemia (AA) children who lack a sibling donor, but the clinical response rate to IST varies. Predictors of response to IST are valuable for stratifying AA patients and making clinical decisions. The serum interleukin (IL)-6 levels of 41 AA patients were measured at the time of diagnosis and the response rate of the patients to IST was evaluated at 3, 6, and 12 months after IST. Receiver-operator characteristic (ROC) analysis was used to calculate the predictive value of initial IL-6 levels in determining response at 6 months after IST. The initial IL-6 levels were significant higher in responders than nonresponders at 6 months after IST (211.89 vs. 18.09 pg/mL; P=0.005), using 36.8 pg/mL as a threshold, there were 80% sensitivity and 81% specificity for discriminating responders and nonresponders to IST. Patients with initial high IL-6 level (>36.8 pg/mL) have favorable response rates than those with initial low IL-6 level (<36.8 pg/mL) at 3, 6, and 12 months after IST (P<0.01). High levels of IL-6 at the time of diagnosis predict a favorable response to IST in children with AA and this may be helpful for patient's stratification and clinical decisions.

  3. Radiographic response to locoregional therapy in hepatocellular carcinoma predicts patient survival times.

    Science.gov (United States)

    Memon, Khairuddin; Kulik, Laura; Lewandowski, Robert J; Wang, Edward; Riaz, Ahsun; Ryu, Robert K; Sato, Kent T; Marshall, Karen; Gupta, Ramona; Nikolaidis, Paul; Miller, Frank H; Yaghmai, Vahid; Senthilnathan, Seanthan; Baker, Talia; Gates, Vanessa L; Abecassis, Michael; Benson, Al B; Mulcahy, Mary F; Omary, Reed A; Salem, Riad

    2011-08-01

    It is not clear whether survival times of patients with hepatocellular carcinoma (HCC) are associated with their response to therapy. We analyzed the association between tumor response and survival times of patients with HCC who were treated with locoregional therapies (LRTs) (chemoembolization and radioembolization). Patients received LRTs over a 9-year period (n = 463). Patients with metastases, portal venous thrombosis, or who had received transplants were excluded; 159 patients with Child-Pugh B7 or lower were analyzed. Response (based on European Association for the Study of the Liver [EASL] and World Health Organization [WHO] criteria) was associated with survival times using the landmark, risk-of-death, and Mantel-Byar methodologies. In a subanalysis, survival times of responders were compared with those of patients with stable disease and progressive disease. Based on 6-month data, in landmark analysis, responders survived longer than nonresponders (based on EASL but not WHO criteria: P = .002 and .0694). The risk of death was also lower for responders (based on EASL but not WHO criteria: P = .0463 and .707). Landmark analysis of 12-month data showed that responders survived longer than nonresponders (P < .0001 and .004, based on EASL and WHO criteria, respectively). The risk of death was lower for responders (P = .0132 and .010, based on EASL and WHO criteria, respectively). By the Mantel-Byar method, responders had longer survival than nonresponders, based on EASL criteria (P < .0001; P = .596 with WHO criteria). In the subanalysis, responders lived longer than patients with stable disease or progressive disease. Radiographic response to LRTs predicts survival time. EASL criteria for response more consistently predicted survival times than WHO criteria. The goal of LRT should be to achieve a radiologic response, rather than to stabilize disease. Copyright © 2011 AGA Institute. Published by Elsevier Inc. All rights reserved.

  4. Assessment of Predictive Response Factors to Intragastric Balloon Therapy for the Treatment of Obesity.

    Science.gov (United States)

    Madeira, Eduardo; Madeira, Miguel; Guedes, Erika Paniago; Mafort, Thiago Thomaz; Neto, Leonardo Vieira; de Oliveira Moreira, Rodrigo; de Pinho, Paulo Roberto Alves; Lopes, Agnaldo José; Farias, Maria Lucia Fleiuss

    2016-03-01

    Obesity is a worldwide epidemic that is difficult to control with non-invasive treatments, which usually present poor results. In this context, the intragastric balloon (IGB) is an important tool that presents a mean body weight loss (BWL) estimated at approximately 12%, although individual responses are highly variable. This study assesses whether there are factors that can predict responses to IGB therapy either before or early after placement of the device. A total of 50 obese patients underwent insertion of IGB placed endoscopically, and patients were monitored for 6 months. The evaluated predictive factors involved general characteristics and psychological, social, and dyspeptic aspects, and the preliminary results obtained in the first month after balloon placement. The mean weight loss was 11.5%, and 48% of the participants presented BWL >10%. Among the factors analyzed before IGB placement, only advanced age (P = .04) and higher scores obtained in the social relationships domain of a shorter version of the World Health Organization's Quality of Life questionnaire (P = .02) were significant. Analysis of the factors evaluated after IGB placement revealed that the BWL amounts observed in week 2 (P = .001) and week 4 (P < .001) and the intensity of dyspeptic symptoms in week 2 (P < .001) were positive predictive factors. The assessment of predictive factors may help to manage patients with IGB.

  5. Cone-beam computed tomography in lung stereotactic ablative radiation therapy: predictive parameters of early response.

    Science.gov (United States)

    Mazzola, Rosario; Fiorentino, Alba; Ricchetti, Francesco; Giaj Levra, Niccolò; Fersino, Sergio; Di Paola, Gioacchino; Lo Casto, Antonio; Ruggieri, Ruggero; Alongi, Filippo

    2016-06-20

    To analyze lung lesion volume variations by contouring on cone-beam CT (CBCT) images to evaluate the early predictive parameters of stereotactic ablative radiation therapy (SABR) treatment response. The prescribed dose of SABR was varied according to the tumour site (central or peripheral) and maximum diameter of the lesions by using a strategy of risk-adapted dose prescription with a dose range between 48 and 70 Gy in 3-10 consecutive fractions. For the purpose of the analysis, the gross tumour volume (GTV) was recontoured for each patient at first and last CBCT using two lung levels/windows: (a) -600/1000 HU and (b) -1000/250 HU. Univariate analysis was performed to evaluate a correlation between lung lesion variations on CBCT using the two levels/windows and treatment response 6 months after SABR. Independent variables were the number of fractions, time between initial and final fraction, biologically effective dose and pre-SABR GTV. Cut points of lesion volume reduction were evaluated to determine the correlation with complete response 6 months after SABR. 41 lung lesions were evaluated. 82 lung lesions were recontoured for each CBCT level/window. A lung lesion shrinkage of at least 20% was revealed to be statistically related to complete response 6 months after SABR for both the CBCT levels/windows used. The probability of complete response ranged between six and eight times higher in respect to CBCT levels/windows -600/1000 HU and -1000/250 HU, respectively, compared with patients without a lesion shrinkage of 20% at the last session of SABR. According to current findings, a lung lesion shrinkage of at least 20% at the last session of SABR could be predictable of complete response 6 months thereafter. Further investigations about this topic are needed. Prediction of the early tumour response could be useful to personalize imaging restaging after the completion of SABR or to incorporate additional therapies in case of poor responders to improve

  6. Quantitative CD3 PET Imaging Predicts Tumor Growth Response to Anti-CTLA-4 Therapy.

    Science.gov (United States)

    Larimer, Benjamin M; Wehrenberg-Klee, Eric; Caraballo, Alexander; Mahmood, Umar

    2016-10-01

    Immune checkpoint inhibitors have made rapid advances, resulting in multiple Food and Drug Administration-approved therapeutics that have markedly improved survival. However, these benefits are limited to a minority subpopulation that achieves a response. Predicting which patients are most likely to benefit would be valuable for individual therapy optimization. T-cell markers such as CD3-by examining active recruitment of the T cells responsible for cancer-cell death-represent a more direct approach to monitoring tumor immune response than pretreatment biopsy or genetic screening. This approach could be especially effective as numerous different therapeutic strategies emerge, decreasing the need for drug-specific biomarkers and instead focusing on T-cell infiltration, which has been previously correlated with treatment response. A CD3 PET imaging agent targeting T cells was synthesized to test the role of such imaging as a predictive marker. The (89)Zr-p-isothiocyanatobenzyl-deferoxamine-CD3 PET probe was assessed in a murine tumor xenograft model of anti-cytotoxic T-lymphocyte antigen-4 (CTLA-4) immunotherapy of colon cancer. Imaging on day 14 revealed 2 distinct groups of mice stratified by PET signal intensity. Although there was no significant difference in tumor volume on the day of imaging, in the high-uptake group subsequent measurements revealed significantly smaller tumors than in either the low-uptake group or the untreated controls. In contrast, there was no significant difference in the size of tumors between the low-uptake and untreated control mice. These findings indicate that high CD3 PET uptake in the anti-CTLA-4-treated mice correlated with subsequent reduced tumor volume and was a predictive biomarker of response. © 2016 by the Society of Nuclear Medicine and Molecular Imaging, Inc.

  7. Germline mutations in DNA repair genes may predict neoadjuvant therapy response in triple negative breast patients.

    Science.gov (United States)

    Spugnesi, Laura; Gabriele, Michele; Scarpitta, Rosa; Tancredi, Mariella; Maresca, Luisa; Gambino, Gaetana; Collavoli, Anita; Aretini, Paolo; Bertolini, Ilaria; Salvadori, Barbara; Landucci, Elisabetta; Fontana, Andrea; Rossetti, Elena; Roncella, Manuela; Naccarato, Giuseppe Antonio; Caligo, Maria Adelaide

    2016-12-01

    Triple negative breast cancers (TNBCs) represent about 15-20% of all breast cancer cases and are characterized by a complex molecular heterogeneity. Some TNBCs exhibit clinical and pathological properties similar to BRCA-mutated tumors, without actually bearing a mutation in BRCA genes. This "BRCAness" phenotype may be explained by germline mutations in other genes involved in DNA repair. Although respond to chemotherapy with alkylating agents, they have a high risk of recurrence and progression. Some studies have shown the efficacy of neoadjuvant therapy in TNBC patients with DNA repair defects, but proper biomarkers of DNA repair deficiency are still needed. Here, we investigated if mutations in DNA repair genes may be correlated with anthracyclines/taxanes neoadjuvant therapy response. DNA from 19 TNBC patients undergoing neoadjuvant therapy were subjected to next generation sequencing of a panel of 24 genes in DNA repair and breast cancer predisposition. In this study, 5 of 19 patients (26%) carried a pathogenic mutation in BRCA1, PALB2, RAD51C and two patients carried a probable pathogenic missense variant. Moreover, VUS (Variants of Unknown Significance) in other genes, predicted to be deleterious by in silico tools, were detected in five patients. Germline mutations in DNA repair genes were found to be associated with the group of TNBC patients who responded to therapy. We conclude that a subgroup of TNBC patients have defects in DNA repair genes, other than BRCA1, and such patients respond favourably to neoadjuvant anthracyclines/taxanes therapy. © 2016 Wiley Periodicals, Inc. © 2016 Wiley Periodicals, Inc.

  8. Predictive cytokine biomarkers of clinical response to glatiramer acetate therapy in multiple sclerosis.

    Science.gov (United States)

    Valenzuela, R M; Kaufman, M; Balashov, K E; Ito, K; Buyske, S; Dhib-Jalbut, S

    2016-11-15

    A prospective study of 62 patients with relapsing-remitting multiple sclerosis (RRMS) treated with Glatiramer acetate (GA) was conducted to evaluate the value of baseline and treatment-modulated cytokines in predicting the clinical response to the drug after 2years of therapy. There were 32 responders and 30 non-responders. GA upregulated Th2/regulatory cytokines and inhibited Th1 cytokines in sera or PBMC supernatants 3 and 6months into treatment. We found two prognostic models with clinical utility. A model based on IL-18 at baseline, the change in TNFa from baseline to 3months, the change in IL-4 from baseline to 6months, and the change in the log of the ratio of TNFa/IL-4 from baseline to 6months had an area under the curve (AUC) of 0.80. A high IL-18 level at baseline and a reduction of TNF-alpha over time are associated with a response to GA. Although the study identified predictive biomarkers of clinical response to GA, the results will need to be validated in other data sets. Copyright © 2016 Elsevier B.V. All rights reserved.

  9. Tumor budding predicts response to anti-EGFR therapies in metastatic colorectal cancer patients

    Science.gov (United States)

    Zlobec, Inti; Molinari, Francesca; Martin, Vittoria; Mazzucchelli, Luca; Saletti, Piercarlo; Trezzi, Rosangela; De Dosso, Sara; Vlajnic, Tatjana; Frattini, Milo; Lugli, Alessandro

    2010-01-01

    AIM: To investigate whether the evaluation of tumor budding can complement K-RAS analysis to improve the individualized prediction of response to anti-epidermal growth factor receptor based therapies in metastatic colorectal cancer (mCRC) patients. METHODS: Forty-three patients with mCRC treated with cetuximab or panitumumab were entered into this study. According to the Response Evaluation Criteria in Solid Tumors criteria, 30 patients had stable or progressive disease (non-responsive), while 13 patients had a partial response. Tumor buds were evaluated from whole tissue sections stained for pan-cytokeratin, evaluated in the densest region using a 40 × objective and “high-grade” tumor budding was defined as 15 buds/high-power field. RESULTS: Tumor buds and K-RAS mutation both correctly classified 68% of patients. All patients with K-RAS mutation (n = 7) or high-grade tumor budding (n = 11) were non-responsive, of which 4 patients had both features. All 13 partial responders were K-RAS wild-type with low-grade tumor budding. Combined, the predictive value of K-RAS and tumor budding was 80%. Additionally, high-grade tumor budding was significantly related to worse progression-free survival [HR (95% CI): 2.8 (1.3-6.0, P = 0.008)]. CONCLUSION: If confirmed in larger cohorts, the addition of tumor budding to K-RAS analysis may represent an effective approach for individualized patient management in the metastatic setting. PMID:20939111

  10. A Framework for Prediction of Response to HCV Therapy Using Different Data Mining Techniques

    Directory of Open Access Journals (Sweden)

    Enas M. F. El Houby

    2014-01-01

    Full Text Available Hepatitis C which is a widely spread disease all over the world is a fatal liver disease caused by Hepatitis C Virus (HCV. The only approved therapy is interferon plus ribavirin. The number of responders to this treatment is low, while its cost is high and side effects are undesirable. Treatment response prediction will help in reducing the patients who suffer from the side effects and high costs without achieving recovery. The aim of this research is to develop a framework which can select the best model to predict HCV patients’ response to the treatment of HCV from clinical information. The framework contains three phases which are preprocessing phase to prepare the data for applying Data Mining (DM techniques, DM phase to apply different DM techniques, and evaluation phase to evaluate and compare the performance of the built models and select the best model as the recommended one. Different DM techniques had been applied which are associative classification, artificial neural network, and decision tree to evaluate the framework. The experimental results showed the effectiveness of the framework in selecting the best model which is the model built by associative classification using histology activity index, fibrosis stage, and alanine amino transferase.

  11. A framework for prediction of response to HCV therapy using different data mining techniques.

    Science.gov (United States)

    El Houby, Enas M F

    2014-01-01

    Hepatitis C which is a widely spread disease all over the world is a fatal liver disease caused by Hepatitis C Virus (HCV). The only approved therapy is interferon plus ribavirin. The number of responders to this treatment is low, while its cost is high and side effects are undesirable. Treatment response prediction will help in reducing the patients who suffer from the side effects and high costs without achieving recovery. The aim of this research is to develop a framework which can select the best model to predict HCV patients' response to the treatment of HCV from clinical information. The framework contains three phases which are preprocessing phase to prepare the data for applying Data Mining (DM) techniques, DM phase to apply different DM techniques, and evaluation phase to evaluate and compare the performance of the built models and select the best model as the recommended one. Different DM techniques had been applied which are associative classification, artificial neural network, and decision tree to evaluate the framework. The experimental results showed the effectiveness of the framework in selecting the best model which is the model built by associative classification using histology activity index, fibrosis stage, and alanine amino transferase.

  12. Alkaline phosphatase predicts response in polycystic liver disease during somatostatin analogue therapy: a pooled analysis

    NARCIS (Netherlands)

    Gevers, T.J.; Nevens, F.; Torres, V.E.; Hogan, M.C.; Drenth, J.P.

    2016-01-01

    BACKGROUND & AIMS: Somatostatin analogues reduce liver volumes in polycystic liver disease. However, patients show considerable variability in treatment responses. Our aim was to identify specific patient, disease or treatment characteristics that predict response in polycystic liver disease during

  13. Genomancy: predicting tumour response to cancer therapy based on the oracle of genetics.

    Science.gov (United States)

    Williams, P D; Lee, J K; Theodorescu, D

    2009-01-01

    Cells are complex systems that regulate a multitude of biologic pathways involving a diverse array of molecules. Cancer can develop when these pathways become deregulated as a result of mutations in the genes coding for these proteins or of epigenetic changes that affect gene expression, or both1,2. The diversity and interconnectedness of these pathways and their molecular components implies that a variety of mutations may lead to tumorigenic cellular deregulation3-6. This variety, combined with the requirement to overcome multiple anticancer defence mechanisms7, contributes to the heterogeneous nature of cancer. Consequently, tumours with similar histology may vary in their underlying molecular circuitry8-10, with resultant differences in biologic behaviour, manifested in proliferation rate, invasiveness, metastatic potential, and unfortunately, response to cytotoxic therapy. Thus, cancer can be thought of as a family of related tumour subtypes, highlighting the need for individualized prediction both of disease progression and of treatment response, based on the molecular characteristics of the tumour.

  14. Radiation therapy for intracranial germ cell tumors. Predictive value of tumor response as evaluated by computed tomography

    Energy Technology Data Exchange (ETDEWEB)

    Ogawa, Kazuhiko; Toita, Takafumi; Kakinohana, Yasumasa; Yamaguchi, Keiichiro; Miyagi, Koichi; Kinjo, Toshihiko; Yamashiro, Katsumi; Sawada, Satoshi [Ryukyu Univ., Nishihara, Okinawa (Japan). School of Medicine

    1997-07-01

    This retrospective study analyzed the outcome in patients with intracranial germ-cell tumors to determine whether tumor response during radiation therapy can predict achievement of primary local with radiation therapy alone. Between 1983 and 1993, 22 patients with untreated primary intracranial germ cell tumors received a total whole brain radiation dose of between 18 Gy and 45 Gy (mean 31.3 Gy) with or without a localized field of 10 to 36.4 Gy (mean, 22.4 Gy), or local irradiation only (1 patient). In 10 patients with pineal tumor only, who were treated first with radiation therapy, tumor response to radiation therapy was evaluated using computed tomography (CT) (at baseline, and approximately 20 Gy and 50 Gy). Areas of calcification in the tumor were subtracted from total tumor volume. Follow-up time ranged from 2 to 12 years. Five-year actuarial survival rates for patients with germinoma were 71%, 100% for patients with a teratoma component, and 100% for patients without histologic verification. Patients with germinomas or tumors suspected of being germinomas who were given more than 50 Gy had no local relapse. There was no correlation between primary local control by radiation therapy alone and initial tumor volume. The rate of tumor volume response to irradiation assessed by CT was significantly different in those patients who relapsed compared to those who did not relapse. Tumor response during radiation therapy using CT was considered to be predictive of primary local control with radiation therapy alone. (author)

  15. Pretreatment prediction of response to peginterferon plus ribavirin therapy in genotype 1 chronic hepatitis C using data mining analysis.

    Science.gov (United States)

    Kurosaki, Masayuki; Sakamoto, Naoya; Iwasaki, Manabu; Sakamoto, Minoru; Suzuki, Yoshiyuki; Hiramatsu, Naoki; Sugauchi, Fuminaka; Yatsuhashi, Hiroshi; Izumi, Namiki

    2011-03-01

    This study aimed to develop a model for the pre-treatment prediction of sustained virological response (SVR) to peg-interferon plus ribavirin therapy in chronic hepatitis C. Data from 800 genotype 1b chronic hepatitis C patients with high viral load (>100,000 IU/ml) treated by peg-interferon plus ribavirin at 6 hospitals in Japan were randomly assigned to a model building (n = 506) or an internal validation (n = 294). Data from 524 patients treated at 29 hospitals in Japan were used for an external validation. Factors predictive of SVR were explored using data mining analysis. Age (predicting the probability of response to therapy with peg-interferon plus ribavirin and has the potential to support clinical decisions regarding the selection of patients for therapy.

  16. Prediction of Response to Medication and Cognitive Therapy in the Treatment of Moderate to Severe Depression

    Science.gov (United States)

    Fournier, Jay C.; DeRubeis, Robert J.; Shelton, Richard C.; Hollon, Steven D.; Amsterdam, Jay D.; Gallop, Robert

    2009-01-01

    A recent randomized controlled trial found nearly equivalent response rates for antidepressant medications and cognitive therapy in a sample of moderate to severely depressed outpatients. In this article, the authors seek to identify the variables that were associated with response across both treatments as well as variables that predicted…

  17. Evolution of nodule stiffness might predict response to local ablative therapy: A series of patients with hepatocellular carcinoma.

    Science.gov (United States)

    Praktiknjo, Michael; Krabbe, Viktoria; Pohlmann, Alessandra; Sampels, Matthias; Jansen, Christian; Meyer, Carsten; Strassburg, Christian P; Trebicka, Jonel; Gonzalez Carmona, Maria A

    2018-01-01

    Early information on treatment response of HCC to local ablative therapy is crucial. Elastography as a non-invasive method has recently been shown to play a potential role in distinguishing between benign and malignant liver lesions. Elastography of hepatocellular carcinoma (HCC) in early response to local ablative therapy has not been studied to date. We prospectively included a cohort of 14 patients with diagnosis of HCC who were treated with local ablative therapy (transarterial chemoembolization, TACE and/or radiofrequency ablation, RFA). We used 2D shear-wave elastography (RT 2D-SWE) to examine stiffness of HCC lesion before and 3, 30 and 90 days after local ablative therapy. Contrast-enhanced imaging after 90 days was performed to evaluate treatment response. Primary endpoint was stiffness of HCC in response to local ablative therapy. Secondary end point was tumor recurrence. Stiffness of HCC nodules and liver showed no significant difference prior to local ablative therapy. As early as three days after treatment, stiffness of responding HCC was significantly higher compared to non-responding. Higher stiffness before treatment was significantly associated with tumor recurrence. Nodule stiffness in general and RT 2D-SWE in particular could provide a useful tool for early prediction of HCC response to local ablative therapy.

  18. Negative Affective Spillover from Daily Events Predicts Early Response to Cognitive Therapy for Depression

    Science.gov (United States)

    Cohen, Lawrence H.; Gunthert, Kathleen C.; Butler, Andrew C.; Parrish, Brendt P.; Wenze, Susan J.; Beck, Judith S.

    2008-01-01

    This study evaluated the predictive role of depressed outpatients' (N = 62) affective reactivity to daily stressors in their rates of improvement in cognitive therapy (CT). For 1 week before treatment, patients completed nightly electronic diaries that assessed daily stressors and negative affect (NA). The authors used multilevel modeling to…

  19. Simple regional strain pattern analysis to predict response to cardiac resynchronization therapy

    DEFF Research Database (Denmark)

    Risum, Niels; Jons, Christian; Olsen, Niels T

    2012-01-01

    A classical strain pattern of early contraction in one wall and prestretching of the opposing wall followed by late contraction has previously been associated with left bundle branch block (LBBB) activation and short-term response to cardiac resynchronization therapy (CRT). Aims of this study were...

  20. The importance of myocardial contractile reserve in predicting response to cardiac resynchronization therapy

    NARCIS (Netherlands)

    Kloosterman, Mariëlle; Damman, Kevin; Van Veldhuisen, Dirk J; Rienstra, Michiel; Maass, Alexander H

    AimTo perform a meta-analysis and systematic review of published data to assess the relationship between contractile reserve and response to cardiac resynchronization therapy (CRT) in patients with heart failure. Methods and resultsWe searched MEDLINE/PubMed and Cochrane for all papers published up

  1. Pattern analysis of defecography in patients with chronic functional constipation: is it predictable for the responsiveness of biofeedback therapy?

    Energy Technology Data Exchange (ETDEWEB)

    Yang, Hye Rin; Kim, Ah Young; Hong, Seong Sook; Byun, Jae Ho; Myung Seung Jae; Ha, Hyun Kwon [University of Ulsan of Medicine, Seoul (Korea, Republic of)

    2005-08-15

    To determine of pattern analysis of defecography can predict the responsiveness of biofeedback therapy in patients with chronic functional constipation. Over a two-year period, 104 patients with chronic functional constipation underwent defecography and biofeedback therapy. Two blinded readers analyzed the defecographic findings and classified them into six types; I = normal defecation, II = hypertonic lower anal sphincter (poor anal opening due to a persistent contraction of the lower anal sphincter), III dyskinetic puborectal sling (inadequate laxity of the puborectal sling), IV spastic pelvic floor syndrome (persistent contraction of both the puborectal sling and the lower and sphincter), V unclassified (including paradoxical contraction of the anal sphincter), VI anatomical obstruction. In addition, the degree of rectal contraction during defecation was scored (grade 0 to 3). After biofeedback therapy, the differences in the defecography patterns or rectal contraction between the two groups, the responsive or non-responsive group, were analyzed. The defecograms revealed that the type IV of the spastic pelvic floor syndrome was most common (50 of 104 patients, 48%), followed by II (21/104, 20%), III (12/104, 11.5%), V (9/104, 9%) and VI (12/104, 11.5%). Biofeedback therapy showed a therapeutic response in 71 out of 104 patients (68%) but failed in 33 patients (32%). However, there were no significant differences in the defecographic pattern between the responsive and non-responsive groups ({rho} = 0.630). The defecograms revealed contractions in 78 patients (75%) and moderate to vigorous contractions (more than grade 2) in 66 patients. Most of the biofeedback-responsive group showed rectal contractions (66 of 71 patients, 93%, {rho} < 0.001). In patients with chronic functional constipation, there was no significant difference in the morphological patterns of the defecogram between the responsive and non-responsive biofeedback groups. However, the presence of

  2. New Perspectives on Predictive Biomarkers of Tumor Response and Their Clinical Application in Preoperative Chemoradiation Therapy for Rectal Cancer.

    Science.gov (United States)

    Kim, Nam Kyu; Hur, Hyuk

    2015-11-01

    Preoperative chemoradiation therapy (CRT) is the standard treatment for patients with locally advanced rectal cancer (LARC) and can improve local control and survival outcomes. However, the responses of individual tumors to CRT are not uniform and vary widely, from complete response to disease progression. Patients with resistant tumors can be exposed to irradiation and chemotherapy that are both expensive and at times toxic without benefit. In contrast, about 60% of tumors show tumor regression and T and N down-staging. Furthermore, a pathologic complete response (pCR), which is characterized by sterilization of all tumor cells, leads to an excellent prognosis and is observed in approximately 10-30% of cases. This variety in tumor response has lead to an increased need to develop a model predictive of responses to CRT in order to identify patients who will benefit from this multimodal treatment. Endoscopy, magnetic resonance imaging, positron emission tomography, serum carcinoembryonic antigen, and molecular biomarkers analyzed using immunohistochemistry and gene expression profiling are the most commonly used predictive models in preoperative CRT. Such modalities guide clinicians in choosing the best possible treatment options and the extent of surgery for each individual patient. However, there are still controversies regarding study outcomes, and a nomogram of combined models of future trends is needed to better predict patient response. The aim of this article was to review currently available tools for predicting tumor response after preoperative CRT in rectal cancer and to explore their applicability in clinical practice for tailored treatment.

  3. Human Papilloma Virus Infection Does Not Predict Response to Interferon Therapy in Ocular Surface Squamous Neoplasia.

    Science.gov (United States)

    Galor, Anat; Garg, Nisha; Nanji, Afshan; Joag, Madhura; Nuovo, Gerard; Palioura, Sotiria; Wang, Gaofeng; Karp, Carol L

    2015-11-01

    To identify the frequency of human papilloma virus (HPV) in ocular surface squamous neoplasia (OSSN) and to evaluate differences in clinical features and treatment response of tumors with positive versus negative HPV results. Retrospective case series. Twenty-seven patients with OSSN. Ocular surface squamous neoplasia specimens were analyzed for the presence of HPV. Clinical features and response to interferon were determined retrospectively and linked to the presence (versus absence) of HPV. Clinical characteristics of OSSN by HPV status. Twenty-one of 27 tumors (78%) demonstrated positive HPV results. The HPV genotypes identified included HPV-16 in 10 tumors (48%), HPV-31 in 5 tumors, HPV-33 in 1 tumor, HPV-35 in 2 tumors, HPV-51 in 2 tumors, and a novel HPV in 3 tumors (total of 23 tumors because 1 tumor had 3 identified genotypes). Tumors found in the superior limbus were more likely to show positive HPV results (48% vs. 0%; P=0.06, Fisher exact test). Tumors with positive HPV-16 results were larger (68 vs. 34 mm2; P=0.08, Mann-Whitney U test) and were more likely to have papillomatous morphologic features (50% vs. 12%; P=0.07, Fisher exact test) compared with tumors showing negative results for HPV-16. Human papilloma virus status was not found to be associated with response to interferon therapy (P=1.0, Fisher exact test). Metrics found to be associated with a nonfavorable response to interferon were male gender and tumors located in the superior conjunctivae. The presence of HPV in OSSN seems to be more common in lesions located in the nonexposed, superior limbus. Human papilloma virus presence does not seem to be required for a favorable response to interferon therapy. Copyright © 2015 American Academy of Ophthalmology. All rights reserved.

  4. Executive function predicts cognitive-behavioral therapy response in childhood obsessive-compulsive disorder

    DEFF Research Database (Denmark)

    Hybel, Katja Anna; Mortensen, Erik Lykke; Lambek, Rikke

    2017-01-01

    Cognitive-behavioral therapy (CBT) is considered first-line treatment for childhood obsessive-compulsive disorder (OCD). Despite CBT's efficacy, too many children and adolescents do not fully respond to treatment, making the identification of predictors of treatment response highly relevant....... Executive functions (EF) have been suggested to constitute such predictors, but studies with pediatric samples are scarce. In the present study, we investigated latent level EF test performance and ratings of daily life EF behavior as predictors of CBT response in pediatric OCD. We further examined....... Daily life EF behavior in OCD probands improved after treatment relative to controls. The findings suggest that EF performance impacts CBT outcome, and that exposure-based CBT is well-suited for children and adolescents with OCD and poorer EF test performance. This study supports the relevance of EF...

  5. Cine dyscontractility index: A novel marker of mechanical dyssynchrony that predicts response to cardiac resynchronization therapy.

    Science.gov (United States)

    Werys, Konrad; Petryka-Mazurkiewicz, Joanna; Błaszczyk, Łukasz; Miśko, Jolanta; Śpiewak, Mateusz; Małek, Łukasz A; Mazurkiewicz, Łukasz; Miłosz-Wieczorek, Barbara; Marczak, Magdalena; Kubik, Agata; Dąbrowska, Agnieszka; Piątkowska-Janko, Ewa; Sawionek, Błażej; Wijesurendra, Rohan; Piechnik, Stefan K; Bogorodzki, Piotr

    2016-12-01

    To investigate whether magnetic resonance imaging (MRI) cine-derived dyssynchrony indices provide additional information compared to conventional tagged MRI (tMRI) acquisitions in heart failure patients undergoing cardiac resynchronization therapy (CRT). Patients scheduled for CRT (n = 52) underwent preprocedure MRI including cine and tMRI acquisitions. Segmental strain curves were calculated for both cine and tMRI to produce a range of standard indices for direct comparison between modalities. We also proposed and evaluated a novel index of "dyscontractility," which detects the presence of focal areas with paradoxically positive circumferential strain. Across conventional strain indices, there was only moderate-to-poor (R = 0.3-0.6) correlation between modalities; eight cine-derived indices showed statistically significant (P cine images (cine dyscontractility index, "CDI") was the single best predictor of clinical response to CRT (area under the curve AUC = 0.81, P Cine-derived strain indices offer potentially new information compared to tMRI. Specifically, the novel CDI is most strongly linked to response to cardiac resynchronization therapy in a contemporary patient cohort. It utilizes readily available MRI data, is relatively straightforward to process, and compares favorably with any conventional tagging index. J. Magn. Reson. Imaging 2016;44:1483-1492. © 2016 International Society for Magnetic Resonance in Medicine.

  6. Serum alpha-fetoprotein response can predict prognosis in hepatocellular carcinoma patients undergoing radiofrequency ablation therapy

    Energy Technology Data Exchange (ETDEWEB)

    Kao, W.-Y. [Division of Gastroenterology, Department of Medicine, Taipei Veterans General Hospital, Taiwan (China); Chiou, Y.-Y., E-mail: yychiou@vghtpe.gov.tw [Department of Radiology, Taipei Veterans General Hospital, Taiwan (China); Faculty of Medicine, School of Medicine, National Yang-Ming University, Taipei, Taiwan (China); Hung, H.-H. [Division of Gastroenterology, Department of Medicine, Taipei Veterans General Hospital, Taiwan (China); Faculty of Medicine, School of Medicine, National Yang-Ming University, Taipei, Taiwan (China); Su, C.-W., E-mail: cwsu2@vghtpe.gov.tw [Division of Gastroenterology, Department of Medicine, Taipei Veterans General Hospital, Taiwan (China); Faculty of Medicine, School of Medicine, National Yang-Ming University, Taipei, Taiwan (China); Institute of Clinical Medicine, School of Medicine, National Yang-Ming University, Taipei, Taiwan (China); Chou, Y.-H. [Department of Radiology, Taipei Veterans General Hospital, Taiwan (China); Faculty of Medicine, School of Medicine, National Yang-Ming University, Taipei, Taiwan (China); Wu, J.-C. [Institute of Clinical Medicine, School of Medicine, National Yang-Ming University, Taipei, Taiwan (China); Department of Medical Research and Education, Taipei Veterans General Hospital, Taiwan (China); Huo, T.-I. [Division of Gastroenterology, Department of Medicine, Taipei Veterans General Hospital, Taiwan (China); Institute of Pharmacology, School of Medicine, National Yang-Ming University, Taipei, Taiwan (China); Huang, Y.-H. [Division of Gastroenterology, Department of Medicine, Taipei Veterans General Hospital, Taiwan (China); Institute of Clinical Medicine, School of Medicine, National Yang-Ming University, Taipei, Taiwan (China); Wu, W.-C. [Division of Gastroenterology, Department of Medicine, Taipei Veterans General Hospital, Taiwan (China)

    2012-05-15

    Aims: To evaluate the clinical inference of serum alpha-fetoprotein (AFP) response in hepatocellular carcinoma (HCC) patients undergoing percutaneous radiofrequency ablation (RFA). Materials and methods: Three hundred and thirteen previously untreated HCC patients were enrolled in the study. The optimal AFP response was defined as >20% decrease from baseline after 1 month of RFA for those with a baseline AFP level of {>=}100 ng/ml. The impact of AFP response on prognosis was analysed and prognostic factors were assessed. Results: After a median follow-up of 26.7 {+-} 19.1 months, 49 patients died and 264 patients were alive. The cumulative 5 year survival rates were 75.3 and 57.4% in patients with an initial AFP of <100 ng/ml and {>=}100 ng/ml, respectively (p = 0.003). In the 58 patients with a baseline AFP of {>=}100 ng/ml and initial completed tumour necrosis after RFA, the cumulative 5 year survival rates were 62.4 and 25.7% in optimal and non-optimal AFP responders, respectively (p = 0.001). By multivariate analysis, the prothrombin time international normalized ratio >1.1 (p = 0.009), non-optimal AFP response (p = 0.023), and creatinine >1.5 mg/dl (p = 0.021) were independent risk factors predictive of poor overall survival. Besides, the cumulative 5 year recurrence rates were 83.4 and 100% in optimal and non-optimal AFP responders, respectively (p < 0.001). Multivariate analysis demonstrated platelet count {<=}10{sup 5}/mm{sup 3} (p = 0.048), tumour size >2 cm (p = 0.027), and non-optimal AFP response (p < 0.001) were independent risk factors associated with tumour recurrence after RFA. Conclusions: Serum AFP response may be a useful marker for predicting prognosis in HCC patients undergoing RFA.

  7. Variants in KCNJ11 and BAD do not predict response to ketogenic dietary therapies for epilepsy.

    Science.gov (United States)

    Schoeler, Natasha E; Leu, Costin; White, Jon; Plagnol, Vincent; Ellard, Sian; Matarin, Mar; Yellen, Gary; Thiele, Elizabeth A; Mackay, Mark; McMahon, Jacinta M; Scheffer, Ingrid E; Sander, Josemir W; Cross, J Helen; Sisodiya, Sanjay M

    2015-12-01

    In the absence of specific metabolic disorders, predictors of response to ketogenic dietary therapies (KDT) are unknown. We aimed to determine whether variants in established candidate genes KCNJ11 and BAD influence response to KDT. We sequenced KCNJ11 and BAD in individuals without previously-known glucose transporter type 1 deficiency syndrome or other metabolic disorders, who received KDT for epilepsy. Hospital records were used to obtain demographic and clinical data. Two response phenotypes were used: ≥ 50% seizure reduction and seizure-freedom at 3-month follow-up. Case/control association tests were conducted with KCNJ11 and BAD variants with minor allele frequency (MAF)>0.01, using PLINK. Response to KDT in individuals with variants with MAF0.01. Eight variants in KCNJ11 and seven in BAD (of which three were previously-unreported) had MAFepilepsy. We can exclude, with 80% power, association from variants with a MAF of >0.05 and effect size >3. A larger sample size is needed to detect associations from rare variants or those with smaller effect sizes. Copyright © 2015 Elsevier B.V. All rights reserved.

  8. Optical coherence tomography: a potential tool for prediction of treatment response for port wine stain after photodynamic therapy

    Science.gov (United States)

    Zhen, Jie; Wang, Chengming; Wang, Ying; Chen, Defu; Gu, Ying

    2014-11-01

    Response of port wine stain (PWS) to photodynamic therapy treatment (PDT) is variable and depends on treatment setting used and anatomic sites as well as on size and depth of ectatic vessels. Optical coherence tomography (OCT) is a non-destructive imaging modality which can reveal the layered structure of the upper part of the skin. The structural features of the PWS skin such as the diameter and depth of the blood vessels in different anatomic sites can be showed in the OCT images. In this study, the possible role of PWS skin structure in the response to PDT is assessed. 82 positions from 43 patients with PWS underwent OCT evaluation in cheek, zygomatic aera, preauricular and temporal region before and 3~4 months after the first PDT when treatment outcomes were also evaluated. After analyzing the structural features in different anatomic sites and the therapeutic effect of them, we found that the ectatic vessels diameter was obvious bigger in the cheek which had slightly poorer outcomes than other areas. Some typical structures had poor or good outcomes after first PDT. These can help the clinic doctors predict the response of some patients which have typical structures after PDT treatment. The OCT will be a potential tool for prediction of treatment response for port wine stain after photodynamic therapy.

  9. Renal Response in Patients with Chronic Kidney Disease Predicts Outcome Following Cardiac Resynchronization Therapy.

    Science.gov (United States)

    Singal, Gaurav; Upadhyay, Gaurav A; Borgquist, Rasmus; Friedman, Daniel J; Chatterjee, Neal A; Kandala, Jagdesh; Park, Mi Young; Orencole, Mary; Dec, George W; Picard, Michael H; Singh, Jagmeet P; Mela, Theofanie

    2015-10-01

    Chronic kidney disease (CKD) severity is associated with increased morbidity and mortality in congestive heart failure. There is a paucity of data regarding renal improvement after cardiac resynchronization therapy (CRT) and its potential impact on clinical outcomes, especially in patients with severe CKD. This was a retrospective analysis of a prospectively collected cohort of 260 patients with CKD undergoing CRT at a single center. Renal function was compared before and after CRT. The primary end point was a composite of death, heart transplant, and left ventricular assist device (LVAD), assessed at 5 years. Patients with more severe CKD demonstrated increased risk of death, transplant, or LVAD following CRT (P = 0.015). Renal response (estimated glomerular filtration rate improvement ≥10 mL/min/1.73 m(2) ) was observed in 14% of all patients and 28% of patients with stage IV CKD. Independent predictors of renal response included left ventricular ejection fraction improvement (odds ratio [OR] 1.06, confidence interval [CI] 1.01-1.10), angiotensin-converting enzyme inhibitor/angiotensin receptor blocker use (OR 4.31, CI 1.08-17.23), and advanced CKD stage (OR 2.19, CI 1.14-4.23). Renal response independently decreased hazard of the primary outcome (HR 0.24, CI 0.08-0.73, P = 0.01). Renal responders with stage IV CKD had 80% 5-year event-free survival, compared to 0% for nonrenal responders in stage IV (P = 0.03). Although severity of CKD is associated with poorer outcome after CRT, improvement in renal function can occur in patients across all CKD stages. Renal responders, including those with stage IV CKD, demonstrate favorable 5-year outcomes. Assessment of renal response may help better prognostic outcomes following CRT. © 2015 Wiley Periodicals, Inc.

  10. Learning from past treatments and their outcome improves prediction of in vivo response to anti-HIV therapy.

    Science.gov (United States)

    Saigo, Hiroto; Altmann, Andre; Bogojeska, Jasmina; Müller, Fabian; Nowozin, Sebastian; Lengauer, Thomas

    2011-01-01

    Infections with the human immunodeficiency virus type 1 (HIV-1) are treated with combinations of drugs. Unfortunately, HIV responds to the treatment by developing resistance mutations. Consequently, the genome of the viral target proteins is sequenced and inspected for resistance mutations as part of routine diagnostic procedures for ensuring an effective treatment. For predicting response to a combination therapy, currently available computer-based methods rely on the genotype of the virus and the composition of the regimen as input. However, no available tool takes full advantage of the knowledge about the order of and the response to previously prescribed regimens. The resulting high-dimensional feature space makes existing methods difficult to apply in a straightforward fashion. The machine learning system proposed in this work, sequence boosting, is tailored to exploiting such high-dimensional information, i.e. the extraction of longitudinal features, by utilizing the recent advancements in data mining and boosting. When applied to predicting the latest treatment outcome for 3,759 treatment-experienced patients from the EuResist integrated database, sequence boosting achieved superior performance compared to SVMs with RBF kernels. Moreover, sequence boosting allows an easy access to the discriminative treatment information. Analysis of feature importance values provided by our model confirmed known facts regarding HIV treatment. For instance, application of potent and recently licensed drugs was beneficial for patients, and, conversely, the patient group that was subject to NRTI mono-therapies in the past had poor treatment perspectives today. Furthermore, our model revealed novel biological insights. More precisely, the combination of previously used drugs with their in vivo response is more informative than the information of previously used drugs alone. Using this information improves the performance of systems for predicting therapy outcome.

  11. Baseline {sup 18}F-FDG PET image-derived parameters for therapy response prediction in oesophageal cancer

    Energy Technology Data Exchange (ETDEWEB)

    Hatt, Mathieu; Visvikis, Dimitris; Cheze-le Rest, Catherine [CHU Morvan, LaTIM, INSERM U650, Brest (France); Pradier, Olivier [CHU Morvan, LaTIM, INSERM U650, Brest (France); CHU Morvan, Department of Radiotherapy, Brest (France)

    2011-09-15

    The objectives of this study were to investigate the predictive value of tumour measurements on 2-deoxy-2-[{sup 18}F]fluoro-D-glucose ({sup 18}F-FDG) positron emission tomography (PET) pretreatment scan regarding therapy response in oesophageal cancer and to evaluate the impact of tumour delineation strategies. Fifty patients with oesophageal cancer treated with concomitant radiochemotherapy between 2004 and 2008 were retrospectively considered and classified as complete, partial or non-responders (including stable and progressive disease) according to Response Evaluation Criteria in Solid Tumors (RECIST). The classification of partial and complete responders was confirmed by biopsy. Tumours were delineated on the {sup 18}F-FDG pretreatment scan using an adaptive threshold and the automatic fuzzy locally adaptive Bayesian (FLAB) methodologies. Several parameters were then extracted: maximum and peak standardized uptake value (SUV), tumour longitudinal length (TL) and volume (TV), SUV{sub mean}, and total lesion glycolysis (TLG = TV x SUV{sub mean}). The correlation between each parameter and response was investigated using Kruskal-Wallis tests, and receiver-operating characteristic methodology was used to assess performance of the parameters to differentiate patients. Whereas commonly used parameters such as SUV measurements were not significant predictive factors of the response, parameters related to tumour functional spatial extent (TL, TV, TLG) allowed significant differentiation of all three groups of patients, independently of the delineation strategy, and could identify complete and non-responders with sensitivity above 75% and specificity above 85%. A systematic although not statistically significant trend was observed regarding the hierarchy of the delineation methodologies and the parameters considered, with slightly higher predictive value obtained with FLAB over adaptive thresholding, and TLG over TV and TL. TLG is a promising predictive factor of

  12. GERD assessment including pH metry predicts a high response rate to PPI standard therapy

    Directory of Open Access Journals (Sweden)

    Kandulski Arne

    2013-01-01

    Full Text Available Abstract Background Inadequate response to proton pump inhibitor (PPI therapy in patients with gastroesophageal reflux disease (GERD is reported in up to 40%. Patients with non erosive reflux disease (NERD have lower response rates compared to patients with erosive reflux disease (ERD; pH metry contributes to GERD diagnosis and is critical for proper diagnosis of NERD. Aim of the study was to assess the need for doubling esomeprazole standard dose (40 mg for 4 weeks in PPI naive patients with typical reflux symptoms and diagnosis of GERD based on endoscopy and 48 hours, wireless pH metry. Methods All patients underwent upper GI endoscopy. Symptoms were recorded with a structured questionnaire (RDQ and acid exposure was determined by 48 hours, wireless pH monitoring (BRAVO. In case of abnormal acid exposure, patients received a short term treatment with esomeprazole 40 mg q.d. for 4 weeks. If symptoms persisted, patients underwent a second pH metry on PPI and the dose was increased to 40 mg b.i.d. Results 31 consecutive patients with typical reflux symptoms underwent 48 hours pH monitoring. 22 patients (71% had abnormal acid exposure, 9 patients had normal pH metry (29%. Of the 9 patients with normal pH metry, 2 were found with erosive esophagitis and 7 without endoscopic abnormalities. 24 patients with documented GERD received esomeprazole treatment. 21 patients achieved complete symptom resolution with 40 mg q.d. after 4 weeks (88%. Only 2 patients required doubling the dose of esomeprazole for complete symptom resolution, 1 patient remained with symptoms. Conclusions Patients with typical reflux symptoms and abnormal acid exposure have a high response rate to standard dose esomeprazole regardless of whether they have ERD or NERD.

  13. Molecular Imaging to Predict Response to Targeted Therapies in Renal Cell Carcinoma

    Directory of Open Access Journals (Sweden)

    Ingrid Leguerney

    2017-01-01

    Full Text Available Molecular magnetic resonance imaging targeted to an endothelial integrin involved in neoangiogenesis was compared to DCE-US and immunochemistry to assess the early response of three different therapeutic agents in renal cell carcinoma. Human A498 renal cells carcinoma was subcutaneously inoculated into 24 nude mice. Mice received either phosphate-buffered saline solution, sunitinib, everolimus, or bevacizumab during 4 days. DCE-US and molecular MRI targeting αvβ3 were performed at baseline and 4 days after treatment initiation. PI, AUC, relaxation rate variations ΔR2⁎, and percentage of vessels area quantified on CD31-stained microvessels were compared. Significant decreases were observed for PI and AUC parameters measured by DCE-US for bevacizumab group as early as 4 days, whereas molecular αvβ3-targeted MRI was able to detect significant changes in both bevacizumab and everolimus groups. Percentage of CD31-stained microvessels was significantly correlated with DCE-US parameters, PI (R=0.87, p=0.0003 and AUC (R=0.81, p=0.0013. The percentage of vessel tissue area was significantly reduced (p<0.01 in both sunitinib and bevacizumab groups. We report an early detection of neoangiogenesis modification after induction of targeted therapies, using DCE-US or αvβ3-targeted MRI. We consider these outcomes should encourage clinical trial developments to further evaluate the potential of this molecular MRI technique.

  14. Predicting treatment response to cognitive behavioral therapy in panic disorder with agoraphobia by integrating local neural information.

    Science.gov (United States)

    Hahn, Tim; Kircher, Tilo; Straube, Benjamin; Wittchen, Hans-Ulrich; Konrad, Carsten; Ströhle, Andreas; Wittmann, André; Pfleiderer, Bettina; Reif, Andreas; Arolt, Volker; Lueken, Ulrike

    2015-01-01

    Although neuroimaging research has made substantial progress in identifying the large-scale neural substrate of anxiety disorders, its value for clinical application lags behind expectations. Machine-learning approaches have predictive potential for individual-patient prognostic purposes and might thus aid translational efforts in psychiatric research. To predict treatment response to cognitive behavioral therapy (CBT) on an individual-patient level based on functional magnetic resonance imaging data in patients with panic disorder with agoraphobia (PD/AG). We included 49 patients free of medication for at least 4 weeks and with a primary diagnosis of PD/AG in a longitudinal study performed at 8 clinical research institutes and outpatient centers across Germany. The functional magnetic resonance imaging study was conducted between July 2007 and March 2010. Twelve CBT sessions conducted 2 times a week focusing on behavioral exposure. Treatment response was defined as exceeding a 50% reduction in Hamilton Anxiety Rating Scale scores. Blood oxygenation level-dependent signal was measured during a differential fear-conditioning task. Regional and whole-brain gaussian process classifiers using a nested leave-one-out cross-validation were used to predict the treatment response from data acquired before CBT. Although no single brain region was predictive of treatment response, integrating regional classifiers based on data from the acquisition and the extinction phases of the fear-conditioning task for the whole brain yielded good predictive performance (accuracy, 82%; sensitivity, 92%; specificity, 72%; P < .001). Data from the acquisition phase enabled 73% correct individual-patient classifications (sensitivity, 80%; specificity, 67%; P < .001), whereas data from the extinction phase led to an accuracy of 74% (sensitivity, 64%; specificity, 83%; P < .001). Conservative reanalyses under consideration of potential confounders yielded nominally lower but comparable

  15. Ventricular pacing site separation by cardiac computed tomography: validation for the prediction of clinical response to cardiac resynchronization therapy.

    Science.gov (United States)

    Modi, S; Yee, Raymond; Scholl, David; Stirrat, John; Wong, Jorge A; Lydell, Carmen; Kotha, Vamshi; Gula, Lorne J; Skanes, Allan C; Leong-Sit, Peter; McCarty, David; Drangova, Maria; White, James A

    2017-09-01

    Cardiac Resynchronization Therapy (CRT) fails to provide benefit in up to one-third of patients. Maximizing the geographic separation of right and left ventricular pacing lead sites has been suggested as one way to improve response. Cardiac CT provides an opportunity to explore 3-dimensional inter-lead distance (ILD) measures for the prediction of CRT response. The objective of this study was to investigate associations between standardized measures of ILD by cardiac CT and echocardiographic response to CRT. Forty-two consecutive patients undergoing CRT had serial clinical and echocardiographic evaluations performed in addition to a post-procedural cardiac-gated CT with blinded measurement of direct and circumferential (via the myocardium) ILD measures. Clinical response to CRT, the primary clinical outcome, was defined as a ≥15% reduction in LVESV using echocardiography at 6-months. The mean age and ejection fraction was 63.6 ± 8.9 years and 25.2 ± 7.8%, respectively. The primary outcome occurred in 35 of 42 patients (83%). Both direct and circumferential CT-based ILD measures were associated with the primary outcome by univariate analysis. Receiver Operator Characteristic analysis identified Circumferential ILD to have the strongest predictive accuracy (AUC 0.78). Inter- and intra-observer reproducibility of CT-derived ILD measures was excellent. Circumferential ILD measures on cardiac CT are predictive of clinical response to CRT. Incorporation of these measures into the selection of optimal pacing targets, particularly from pre-procedural CT coronary vein imaging may be of therapeutic benefit and warrants further investigation.

  16. Impairments in goal-directed actions predict treatment response to cognitive-behavioral therapy in social anxiety disorder.

    Directory of Open Access Journals (Sweden)

    Gail A Alvares

    Full Text Available Social anxiety disorder is characterized by excessive fear and habitual avoidance of social situations. Decision-making models suggest that patients with anxiety disorders may fail to exhibit goal-directed control over actions. We therefore investigated whether such biases may also be associated with social anxiety and to examine the relationship between such behavior with outcomes from cognitive-behavioral therapy. Patients diagnosed with social anxiety and controls completed an instrumental learning task in which two actions were performed to earn food outcomes. After outcome devaluation, where one outcome was consumed to satiety, participants were re-tested in extinction. Results indicated that, as expected, controls were goal-directed, selectively reducing responding on the action that previously delivered the devalued outcome. Patients with social anxiety, however, exhibited no difference in responding on either action. This loss of a devaluation effect was associated with greater symptom severity and poorer response to therapy. These findings indicate that variations in goal-directed control in social anxiety may represent both a behavioral endophenotype and may be used to predict individuals who will respond to learning-based therapies.

  17. Impairments in goal-directed actions predict treatment response to cognitive-behavioral therapy in social anxiety disorder.

    Science.gov (United States)

    Alvares, Gail A; Balleine, Bernard W; Guastella, Adam J

    2014-01-01

    Social anxiety disorder is characterized by excessive fear and habitual avoidance of social situations. Decision-making models suggest that patients with anxiety disorders may fail to exhibit goal-directed control over actions. We therefore investigated whether such biases may also be associated with social anxiety and to examine the relationship between such behavior with outcomes from cognitive-behavioral therapy. Patients diagnosed with social anxiety and controls completed an instrumental learning task in which two actions were performed to earn food outcomes. After outcome devaluation, where one outcome was consumed to satiety, participants were re-tested in extinction. Results indicated that, as expected, controls were goal-directed, selectively reducing responding on the action that previously delivered the devalued outcome. Patients with social anxiety, however, exhibited no difference in responding on either action. This loss of a devaluation effect was associated with greater symptom severity and poorer response to therapy. These findings indicate that variations in goal-directed control in social anxiety may represent both a behavioral endophenotype and may be used to predict individuals who will respond to learning-based therapies.

  18. T-wave area predicts response to cardiac resynchronization therapy in patients with left bundle branch block.

    Science.gov (United States)

    Engels, Elien B; Végh, Eszter M; Van Deursen, Caroline J M; Vernooy, Kevin; Singh, Jagmeet P; Prinzen, Frits W

    2015-02-01

    Chronic heart failure patients with a left ventricular (LV) conduction delay, mostly due to left bundle branch block (LBBB), generally derive benefit from cardiac resynchronization therapy (CRT). However, 30-50% of patients do not show a clear response to CRT. We investigated whether T-wave analysis of the ECG can improve patient selection. The study population comprised 244 CRT recipients with baseline 12-lead electrocardiogram recordings. Echocardiographic response after 6-month CRT was defined as a ≥5% increase in LV ejection fraction (LVEF). Vectorcardiograms (VCGs) were constructed from the measured 12-lead ECGs using an adapted Kors algorithm on digitized ECGs. Logistic regression models indicated repolarization variables as good predictors of CRT response. The VCG-derived T-wave area predicted CRT response (odds ratio [OR] per 10 μVs increase 1.172 [P < 0.001]) even better than QRS-wave area (OR = 1.116 [P = 0.001]). T-wave area had especially predictive value in the LBBB patient group (OR = 2.77 in LBBB vs. 1.09 in non-LBBB). This predictive value persisted after adjustment of multiple covariates, such as gender, ischemia, age, hypertension, coronary artery bypass graft, and the usage of diuretics and β-blockers. In LBBB patients, the increase in LVEF was 6.1 ± 9.7% and 11.3 ± 9.1% in patients with T-wave area below and above the median value, respectively (P < 0.01). In patients with LBBB morphology of the QRS complex, a larger baseline T-wave area is an important independent predictor of LVEF increase following CRT. © 2014 Wiley Periodicals, Inc.

  19. Robustness of intratumour {sup 18}F-FDG PET uptake heterogeneity quantification for therapy response prediction in oesophageal carcinoma

    Energy Technology Data Exchange (ETDEWEB)

    Hatt, Mathieu; Tixier, Florent; Visvikis, Dimitris [CHRU Morvan, INSERM, UMR 1101, LaTIM, Brest (France); Cheze Le Rest, Catherine [CHU Miletrie, Nuclear Medicine, Poitiers (France); Pradier, Olivier [CHRU Morvan, Radiotherapy, Brest (France)

    2013-10-15

    Intratumour uptake heterogeneity in PET quantified in terms of textural features for response to therapy has been investigated in several studies, including assessment of their robustness for reconstruction and physiological reproducibility. However, there has been no thorough assessment of the potential impact of preprocessing steps on the resulting quantification and its predictive value. The goal of this work was to assess the robustness of PET heterogeneity in textural features for delineation of functional volumes and partial volume correction (PVC). This retrospective analysis included 50 patients with oesophageal cancer. PVC of each PET image was performed. Tumour volumes were determined using fixed and adaptive thresholding, and the fuzzy locally adaptive Bayesian algorithm, and heterogeneity was quantified using local and regional textural features. Differences in the absolute values of the image-derived parameters considered were assessed using Bland-Altman analysis. The impact on their predictive value for the identification of patient nonresponders was assessed by comparing areas under the receiver operating characteristic curves. Heterogeneity parameters were more dependent on delineation than on PVC. The parameters most sensitive to delineation and PVC were regional ones (intensity variability and size zone variability), whereas local parameters such as entropy and homogeneity were the most robust. Despite the large differences in absolute values obtained from different delineation methods or after PVC, these differences did not necessarily translate into a significant impact on their predictive value. Parameters such as entropy, homogeneity, dissimilarity (for local heterogeneity characterization) and zone percentage (for regional characterization) should be preferred. This selection is based on a demonstrated high differentiation power in terms of predicting response, as well as a significant robustness with respect to the delineation method used

  20. Behavioral factors for predicting severity of enuresis and treatment responses in different compliance groups receiving behavioral therapy

    Science.gov (United States)

    Ma, Yanli; Liu, Xiaomei; Shen, Ying

    2017-01-01

    Objective: To investigate behavioral factors for predicting severity of nocturnal enuresis and compare response rates in different compliance groups of behavioral interventions. Methods: Three hundred eleven children diagnosed with nocturnal enuresis were enrolled. This study was conducted at Beijing Children’s Hospital affiliated to the Capital Medical University from September 2016 to December 2016. Correlation of severity of enuresis and behavioral factors was investigated. All patients were treated with desmopressin based on behavioral interventions. After twomonth treatment, the patients were grouped according to the compliance of behavioral therapy. Then response rates in different compliance groups were compared. Results: Multivariate analysis revealed stool frequency, drinking water before going to bed, awaking the child to toilet at night, and appetite were independent risk factors affecting the severity of enuresis. The complete response rate of enuresis and partial response ratein fullcompliance group are higher than thoseof partial compliance and non-compliance group(21.9% vs 11.3%, 78.1% vs 59.8%; 21.9% vs 0%, 78.1% vs 49.1%; Penuresis. Good compliance of behavioral interventions may have a crucial role for better therapeutic outcomes. PMID:29067072

  1. Neural markers of attention to aversive pictures predict response to cognitive behavioral therapy in anxiety and depression.

    Science.gov (United States)

    Stange, Jonathan P; MacNamara, Annmarie; Barnas, Olga; Kennedy, Amy E; Hajcak, Greg; Phan, K Luan; Klumpp, Heide

    2017-02-01

    Excessive attention toward aversive information may be a core mechanism underlying emotional disorders, but little is known about whether this is predictive of response to treatments. We evaluated whether enhanced attention toward aversive stimuli, as indexed by an event-related potential component, the late positive potential (LPP), would predict response to cognitive behavioral therapy (CBT) in patients with social anxiety disorder and/or major depressive disorder. Thirty-two patients receiving 12 weeks of CBT responded to briefly-presented pairs of aversive and neutral pictures that served as targets or distracters while electroencephaolography was recorded. Patients with larger pre-treatment LPPs to aversive relative to neutral distracters (when targets were aversive) were more likely to respond to CBT, and demonstrated larger reductions in symptoms of depression and anxiety following treatment. Increased attention toward irrelevant aversive stimuli may signal attenuated top-down control, so treatments like CBT that improve this control could be beneficial for these individuals. Copyright © 2016 Elsevier B.V. All rights reserved.

  2. What good are positive emotions for treatment? Trait positive emotionality predicts response to Cognitive Behavioral Therapy for anxiety.

    Science.gov (United States)

    Taylor, Charles T; Knapp, Sarah E; Bomyea, Jessica A; Ramsawh, Holly J; Paulus, Martin P; Stein, Murray B

    2017-06-01

    Cognitive behavioral therapy (CBT) is empirically supported for the treatment of anxiety disorders; however, not all individuals achieve recovery following CBT. Positive emotions serve a number of functions that theoretically should facilitate response to CBT - they promote flexible patterns of information processing and assimilation of new information, encourage approach-oriented behavior, and speed physiological recovery from negative emotions. We conducted a secondary analysis of an existing clinical trial dataset to test the a priori hypothesis that individual differences in trait positive emotions would predict CBT response for anxiety. Participants meeting diagnostic criteria for panic disorder (n = 28) or generalized anxiety disorder (n = 31) completed 10 weekly individual CBT sessions. Trait positive emotionality was assessed at pre-treatment, and severity of anxiety symptoms and associated impairment was assessed throughout treatment. Participants who reported a greater propensity to experience positive emotions at pre-treatment displayed the largest reduction in anxiety symptoms as well as fewer symptoms following treatment. Positive emotions remained a robust predictor of change in symptoms when controlling for baseline depression severity. Initial evidence supports the predictive value of trait positive emotions as a prognostic indicator for CBT outcome in a GAD and PD sample. Copyright © 2017 Elsevier Ltd. All rights reserved.

  3. Amygdala response predicts trajectory of symptom reduction during Trauma-Focused Cognitive-Behavioral Therapy among adolescent girls with PTSD.

    Science.gov (United States)

    Cisler, Josh M; Sigel, Benjamin A; Kramer, Teresa L; Smitherman, Sonet; Vanderzee, Karin; Pemberton, Joy; Kilts, Clinton D

    2015-12-01

    Trauma-Focused Cognitive-Behavioral Therapy (TF-CBT) is the gold standard treatment for pediatric PTSD. Nonetheless, clinical outcomes in TF-CBT are highly variable, indicating a need to identify reliable predictors that allow forecasting treatment response. Here, we test the hypothesis that functional neuroimaging correlates of emotion processing predict PTSD symptom reduction during Trauma-Focused Cognitive-Behavioral Therapy (TF-CBT) among adolescent girls with PTSD. Thirty-four adolescent girls with PTSD related to physical or sexual assault were enrolled in TF-CBT, delivered in an approximately 12 session format, in an open trial. Prior to treatment, they were engaged in an implicit threat processing task during 3T fMRI, during which they viewed faces depicting fearful or neutral expressions. Among adolescent girls completing TF-CBT (n = 23), slopes of PTSD symptom trajectories during TF-CBT were significantly related to pre-treatment degree of bilateral amygdala activation while viewing fearful vs neutral images. Adolescents with less symptom reduction were characterized by greater amygdala activation to both threat and neutral images (i.e., less threat-safety discrimination), whereas adolescents with greater symptom reduction were characterized by amygdala activation only to threat images. These clinical outcome relationships with pre-treatment bilateral amygdala activation remained when controlling for possible confounding demographic or clinical variables (e.g., concurrent psychotropic medication, comorbid diagnoses). While limited by a lack of a control group, these preliminary results suggest that pre-treatment amygdala reactivity to fear stimuli, a component of neurocircuitry models of PTSD, positively predicts symptom reduction during TF-CBT among assaulted adolescent girls, providing support for an objective measure for forecasting treatment response in this vulnerable population. Copyright © 2015 Elsevier Ltd. All rights reserved.

  4. Low value of simple echocardiographic indices of ventricular dyssynchrony in predicting the response to cardiac resynchronization therapy.

    Science.gov (United States)

    Bordachar, Pierre; Lafitte, Stéphane; Réant, Patricia; Reuter, Sylvain; Clementy, Jacques; Mletzko, Ralph-Uwe; Siegel, Robert M; Goscinska-Bis, Kinga; Bowes, Robert; Morgan, John; Bénard, Sandrine; Leclercq, Christophe

    2010-06-01

    A recent study suggested that no single echocardiographic index of cardiac dyssynchrony can reliably identify candidates for cardiac resynchronization therapy (CRT). We examined the value of three simple echocardiographic indices for predicting the 6-month clinical and echocardiographic responses to CRT. We analysed data from 75 CRT-D system recipients. Standard echocardiography was used to measure aortic pre-ejection delay (APED), interventricular mechanical delay (IVMD), and delayed activation of the left ventricular (LV) infero-lateral wall (OVERLAP). Clinical responders were defined as patients who had an improved status, based on rehospitalization for heart failure, NYHA class, and peak oxygen consumption. Echocardiographic responders had a > or =10% decrease in LV end-systolic volume. During the study, one patient died and five were lost to follow-up. Of the remaining 69 analysable patients, 50 (72.5%) were classed as clinical responders and 41 (59.4%) as echocardiographic responders to CRT. Before CRT implantation, APED, IVMD, and OVERLAP were similar in responders and non-responders. The value of these indices of dyssynchrony as single or combined predictors of the clinical or echocardiographic response to CRT was low, with sensitivities ranging between 4 and 63%, and specificities between 37 and 100%. Simple echocardiographic indices of dyssynchrony were poor predictors of response to CRT.

  5. Epigenetic Regulation of KLHL34 Predictive of Pathologic Response to Preoperative Chemoradiation Therapy in Rectal Cancer Patients

    Energy Technology Data Exchange (ETDEWEB)

    Ha, Ye J. [Department of Surgery, University of Ulsan College of Medicine, Seoul (Korea, Republic of); Institute of Innovative Cancer Research and Asan Institute for Life Sciences, Asan Medical Center, Seoul (Korea, Republic of); Kim, Chan W. [Department of Surgery, University of Ulsan College of Medicine, Seoul (Korea, Republic of); Roh, Seon A. [Department of Surgery, University of Ulsan College of Medicine, Seoul (Korea, Republic of); Institute of Innovative Cancer Research and Asan Institute for Life Sciences, Asan Medical Center, Seoul (Korea, Republic of); Cho, Dong H. [Institute of Innovative Cancer Research and Asan Institute for Life Sciences, Asan Medical Center, Seoul (Korea, Republic of); Graduate School of East-West Medical Science, Kyung Hee University, Gyeonggi-do (Korea, Republic of); Park, Jong L.; Kim, Seon Y. [Medical Genomics Research Center, Korea Research Institute of Bioscience & Biotechnology, Daejeon (Korea, Republic of); Kim, Jong H. [Department of Radiation Oncology, University of Ulsan College of Medicine, Seoul (Korea, Republic of); Choi, Eun K. [Department of Radiation Oncology, University of Ulsan College of Medicine, Seoul (Korea, Republic of); Institute of Innovative Cancer Research and Asan Institute for Life Sciences, Asan Medical Center, Seoul (Korea, Republic of); Kim, Yong S., E-mail: yongsung@kribb.re.kr [Medical Genomics Research Center, Korea Research Institute of Bioscience & Biotechnology, Daejeon (Korea, Republic of); Institute of Innovative Cancer Research and Asan Institute for Life Sciences, Asan Medical Center, Seoul (Korea, Republic of); Kim, Jin C., E-mail: jckim@amc.seoul.kr [Department of Surgery, University of Ulsan College of Medicine, Seoul (Korea, Republic of); Institute of Innovative Cancer Research and Asan Institute for Life Sciences, Asan Medical Center, Seoul (Korea, Republic of)

    2015-03-01

    Purpose: Prediction of individual responsiveness to preoperative chemoradiation therapy (CRT) is urgently needed in patients with poorly responsive locally advanced rectal cancer (LARC). Methods and Materials: Candidate methylation genes associated with radiosensitivity were identified using a 3-step process. In the first step, genome-wide screening of methylation genes was performed in correlation with histopathologic tumor regression grade in 45 patients with LARC. In the second step, the methylation status of selected sites was analyzed by pyrosequencing in 67 LARC patients, including 24 patients analyzed in the first step. Finally, colorectal cancer cell clones with stable KLHL34 knockdown were generated and tested for cellular sensitivity to radiation. Results: Genome-wide screening identified 7 hypermethylated CpG sites (DZIP1 cg24107021, DZIP1 cg26886381, ZEB1 cg04430381, DKK3 cg041006961, STL cg00991794, KLHL34 cg01828474, and ARHGAP6 cg07828380) associated with preoperative CRT responses. Radiosensitivity in patients with hypermethylated KLHL34 cg14232291 was confirmed by pyrosequencing in additional cohorts. Knockdown of KLHL34 significantly reduced colony formation (KLHL34 sh#1: 20.1%, P=.0001 and KLHL34 sh#2: 15.8%, P=.0002), increased the cytotoxicity (KLHL34 sh#1: 14.8%, P=.019 and KLHL34 sh#2: 17.9%, P=.007) in LoVo cells, and increased radiation-induced caspase-3 activity and the sub-G1 population of cells. Conclusions: The methylation status of KLHL34 cg14232291 may be a predictive candidate of sensitivity to preoperative CRT, although further validation is needed in large cohorts using various cell types.

  6. Predictive Value of PTEN and AR Coexpression of Sustained Responsiveness to Hormonal Therapy in Prostate Cancer—A Pilot Study

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    Soha Salama El Sheikh

    2008-09-01

    Full Text Available One limitation of current biochemical or histologic analysis of advanced prostate cancer (PC; T3/T4 ±Nx Mx is the ability to identify on first diagnostic biopsy patients who will make a durable response to hormone ablation therapy. The aim of this study was to assess the predictive value (sustained response to hormonal therapy and clinical outcome (relapse-free and overall survival of phosphatase and tensin homolog (PTEN and the androgen receptor (AR immunoexpression in the presenting biopsy. Analysis was performed on 47 samples (10 cases of benign prostatic hyperplasia and 37 hormone-naive PCs. Patients selected represented two stages in the natural history of PC: The “clinical metastatic androgen–responsive” (androgen-dependent PC, ADPC and the “clinical metastatic androgen–resistant” (androgen-independent PC, AIPC. Reduced immunoreactivity (IR of either or both PTEN/AR in the initial hormone-naive PC samples was observed with increased frequency in AIPCs. In the ADPC group, low PTEN and/or AR-IR was associated with a shorter median relapse-free survival, i.e., at 30 months after surgery, the probability of relapse-free survival for high expressors of PTEN and AR was 85.7% (SEM = 9.3 compared with only 16.6% (SEM = 15.2 in low expressors. At 36 months, only 28.5% (SEM = 9.3 of ADPC high expressors had experienced a biochemical relapse compared with 100% of low expressors (hazard ratio, 4.6; 95% confidence interval, 4.7-146.8. Further studies analyzing the coexpression of PTEN and AR should be undertaken to validate this pilot study and the utility of these biomarkers in routine histopathologic workup of patients with PC.

  7. Multidetector-computed tomography attenuation values between the tumor and aortic wall in response to induction therapy for esophageal cancer and its predictive value for aortic invasion.

    Science.gov (United States)

    Tsujimoto, Hironori; Ichikura, Takashi; Aiko, Satoshi; Yaguchi, Yoshihisa; Kumano, Isao; Takahata, Risa; Matsumoto, Yusuke; Yoshida, Kazumichi; Ono, Satoshi; Yamamoto, Junji; Hase, Kazuo

    2012-02-01

    The objective of this study was to evaluate the multidetector computed tomography (MDCT) attenuation value between the tumor and aorta in response to the induction therapy for esophageal cancer. In advanced esophageal cancer, the main reason for unresectability is the local invasion of the tumor into the aorta or trachea. Despite remarkable advances in diagnostic modalities, pre-operative assessment of pathological response and local tumor extent in esophageal cancer remains difficult. MDCT attenuation values between the tumor and aorta, and the contact angle of the tumor to the aorta (Picus' angle) were retrospectively evaluated in patients with esophageal cancer who underwent induction therapy in terms of predicting the pathological response, aortic invasion and prognosis of esophageal cancer. The induction therapy may increase the tumor-to-aorta distance and decrease the maximum tumor size and Picus' angle. When the tumor-to-aorta cut-off value was set at 1.3 mm following therapy and underwent curative resection. The assessment of the MDCT attenuation value between the esophageal tumor and the aorta is simple and objectively assesses the response to the induction therapy and aortic invasion in esophageal cancer. This method should be applied to predict the response to the induction therapy and to prevent unnecessary surgery in patients with tumors involving the aorta.

  8. Strong anti-Epstein Barr virus (EBV or cytomegalovirus (CMV cellular immune responses predict survival and a favourable response to anti-tuberculosis therapy

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    Tumaini Nagu

    2017-03-01

    Conclusions: Increased cellular immune responses to CMV and EBV antigens at the time of diagnosis of pulmonary tuberculosis are associated with increased survival after a standard six months anti-TB therapy. CVM and EBV antigens may represent “intrinsic markers for immune fitness” and guide improved TB therapies including host-directed therapies.

  9. An Integrative Model of Physiological Traits Can be Used to Predict Obstructive Sleep Apnea and Response to Non Positive Airway Pressure Therapy

    Science.gov (United States)

    Owens, Robert L.; Edwards, Bradley A.; Eckert, Danny J.; Jordan, Amy S.; Sands, Scott A.; Malhotra, Atul; White, David P.; Loring, Stephen H.; Butler, James P.; Wellman, Andrew

    2015-01-01

    Study Objectives: Both anatomical and nonanatomical traits are important in obstructive sleep apnea (OSA) pathogenesis. We have previously described a model combining these traits, but have not determined its diagnostic accuracy to predict OSA. A valid model, and knowledge of the published effect sizes of trait manipulation, would also allow us to predict the number of patients with OSA who might be effectively treated without using positive airway pressure (PAP). Design, Participants and Intervention: Fifty-seven subjects with and without OSA underwent standard clinical and research sleep studies to measure OSA severity and the physiological traits important for OSA pathogenesis, respectively. The traits were incorporated into a physiological model to predict OSA. The model validity was determined by comparing the model prediction of OSA to the clinical diagnosis of OSA. The effect of various trait manipulations was then simulated to predict the proportion of patients treated by each intervention. Measurements and Results: The model had good sensitivity (80%) and specificity (100%) for predicting OSA. A single intervention on one trait would be predicted to treat OSA in approximately one quarter of all patients. Combination therapy with two interventions was predicted to treat OSA in ∼50% of patients. Conclusions: An integrative model of physiological traits can be used to predict population-wide and individual responses to non-PAP therapy. Many patients with OSA would be expected to be treated based on known trait manipulations, making a strong case for the importance of non-anatomical traits in OSA pathogenesis and the effectiveness of non-PAP therapies. Citation: Owens RL, Edwards BA, Eckert DJ, Jordan AS, Sands SA, Malhotra A, White DP, Loring SH, Butler JP, Wellman A. An integrative model of physiological traits can be used to predict obstructive sleep apnea and response to non positive airway pressure therapy. SLEEP 2015;38(6):961–970. PMID:25515107

  10. Stereotactic Ablative Radiation Therapy for Lung Oligometastases: Predictive Parameters of Early Response by 18FDG-PET/CT.

    Science.gov (United States)

    Mazzola, Rosario; Fiorentino, Alba; Di Paola, Gioacchino; Giaj Levra, Niccolò; Ricchetti, Francesco; Fersino, Sergio; Tebano, Umberto; Pasetto, Stefano; Ruggieri, Ruggero; Salgarello, Matteo; Alongi, Filippo

    2017-03-01

    The objective of this study was to investigate fludeoxyglucose F 18 positron emission tomography/computed tomography (18FDG-PET/CT) parameters as predictive of response after stereotactic ablative radiotherapy (SABR) for lung oligometastases. The inclusion criteria of the current retrospective study were as follows: (1) lung oligometastases treated by SABR, (2) presence of 18FDG-PET/CT before and after SABR for at least two subsequent evaluations, (3) Karnofsky performance status higher than 80, and (4) life expectancy longer than 6 months. All patients were treated with a biologically equivalent dose of at least 100 Gy with an alpha/beta ratio of 10. The following metabolic parameters were semiquantitatively defined: maximum standardized uptake value (SUVmax), mean standardized uptake value (SUVmean), metabolic tumor volume, and total lesion glycolysis. A total of 50 patients met the inclusion criteria, for a total of 70 lung metastases. The pre-SABR median SUVmax was 6.5 (range 4-17), the median SUVmean was 3.7 (range 2.5-6.5), and the median metabolic tumor volume was 2.3 cm3 (0.2-31 cm3). The following metabolic parameters were significantly related to complete response at 6 months: SUVmax less than 5 (p < 0.001) and SUVmean less than 3.5 (p = 0.03). ΔSUVmax at 3 to 6 months was +126% for lesions with in-field progression versus -26% for the remaining lesions (p = 0.002). ΔSUVmean at 3 to 6 months was +15% for lesions with in-field progression versus -26% for the remaining metastases (p = 0.008). In the current analysis, complete response from lung metastasis at 6 months after stereotactic body radiation therapy was significantly associated with both the maximum and mean values of pre-SABR 18FDG-PET/CT SUV. Longer-term trials are strongly advocated to improve the personalization of the monitoring of tumor response in patients with lung oligometastases and, consequently, monitoring of the cost-effectiveness of the health care. Copyright © 2016 International

  11. Type I interferon receptor in peripheral blood mononuclear cells may predict response to intra-arterial 5-fluorouracil + interferon therapy for advanced hepatocellular carcinoma

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    Korenaga K

    2011-04-01

    Full Text Available Yasuyuki Tomiyama1, Naoko Yoshioka1, Yoshiaki Yanai2,3, Tomoya Kawase1, Sohji Nishina1, Yuichi Hara1, Koji Yoshida1, Keiko Korenaga1, Masaaki Korenaga1, Keisuke Hino11Department of Hepatology and Pancreatology, Kawasaki Medical University, Kurashiki, Japan; 2Institute of Fujisaki, Hayashibara Biochemical Lab Inc, Okayama, Japan; 3Pharmaceutical Marketing Division, Otsuka Pharmaceutical Co Ltd, Tokyo, JapanBackground: Type 1 interferon alpha receptor 2 (IFNAR2 in the liver has been reported to be a predictive factor for the response to intra-arterial 5-fluorouracil (5-FU + systemic interferon (IFN-alpha combination therapy in patients with advanced hepatocellular carcinoma. We tested whether IFNAR2 expression in peripheral blood mononuclear cells could predict the response to 5-FU + IFN.Methods: Predictive factors for survival and response to therapy were determined in 30 patients with advanced hepatocellular carcinoma who underwent treatment with 5-FU + IFN. IFNAR2 expression in peripheral blood mononuclear cells was measured in 11 of the 30 patients.Results: With a mean number of 4.2 courses of combination therapy, one patient (3% showed a complete response, eight (27% showed partial responses, 13 (43% had stable disease, and eight (27% showed progressive disease. The median survival time of responders (complete response/partial response was 12.7 months and that of nonresponders (stable disease/progressive disease was 7.5 months. The one-year and two-year cumulative survival rates of responders and nonresponders were 87/69% and 40/11%, respectively (P = 0.019. Multivariate analysis identified response to therapy (P = 0.037 as the sole independent determinant of survival. The expression level of IFNAR2 in peripheral blood mononuclear cells was significantly (P = 0.012 higher in responders (6.5 ± 2.4 than in nonresponders (2.4 ± 0.6, even though no clinical factors were identified as being associated with the response to the combination

  12. Potential Impact of a Free Online HIV Treatment Response Prediction System for Reducing Virological Failures and Drug Costs after Antiretroviral Therapy Failure in a Resource-Limited Setting

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    Andrew D. Revell

    2013-01-01

    Full Text Available Objective. Antiretroviral drug selection in resource-limited settings is often dictated by strict protocols as part of a public health strategy. The objective of this retrospective study was to examine if the HIV-TRePS online treatment prediction tool could help reduce treatment failure and drug costs in such settings. Methods. The HIV-TRePS computational models were used to predict the probability of response to therapy for 206 cases of treatment change following failure in India. The models were used to identify alternative locally available 3-drug regimens, which were predicted to be effective. The costs of these regimens were compared to those actually used in the clinic. Results. The models predicted the responses to treatment of the cases with an accuracy of 0.64. The models identified alternative drug regimens that were predicted to result in improved virological response and lower costs than those used in the clinic in 85% of the cases. The average annual cost saving was $364 USD per year (41%. Conclusions. Computational models that do not require a genotype can predict and potentially avoid treatment failure and may reduce therapy costs. The use of such a system to guide therapeutic decision-making could confer health economic benefits in resource-limited settings.

  13. Predicting response to cognitive therapy and interpersonal therapy, with or without antidepressant medication, for major depression: a pragmatic trial in routine practice

    NARCIS (Netherlands)

    Huibers, M.J.H.; van Breukelen, G.; Roelofs, J.; Hollon, S.D.; Markowitz, J.C.; van Os, J.; Arntz, A.; Peeters, F.

    2014-01-01

    Background: Identifying patient characteristics that predict response within treatments (prognostic) or between treatments (prescriptive) can inform clinical decision-making. In this study, we sought to identify predictors of response to evidence-based treatments in a sample of depressed patients

  14. Specific lymphocyte subsets predict response to adoptive cell therapy using expanded autologous tumor-infiltrating lymphocytes in metastatic melanoma patients

    Science.gov (United States)

    Radvanyi, Laszlo G.; Bernatchez, Chantale; Zhang, Minying; Fox, Patricia S.; Miller, Priscilla; Chacon, Jessica; Wu, Richard; Lizee, Gregory; Mahoney, Sandy; Alvarado, Gladys; Glass, Michelle; Johnson, Valen E.; McMannis, John D.; Shpall, Elizabeth; Prieto, Victor; Papadopoulos, Nicholas; Kim, Kevin; Homsi, Jade; Bedikian, Agop; Hwu, Wen-Jen; Patel, Sapna; Ross, Merrick I.; Lee, Jeffrey E.; Gershenwald, Jeffrey E.; Lucci, Anthony; Royal, Richard; Cormier, Janice N.; Davies, Michael A.; Mansaray, Rahmatu; Fulbright, Orenthial J.; Toth, Christopher; Ramachandran, Renjith; Wardell, Seth; Gonzalez, Audrey; Hwu, Patrick

    2012-01-01

    Purpose Adoptive cell therapy (ACT) using autologous tumor-infiltrating lymphocytes (TIL) is a promising treatment for metastatic melanoma unresponsive to conventional therapies. We report here on the results of an ongoing Phase II clinical trial testing the efficacy of ACT using TIL in metastatic melanoma patients and the association of specific patient clinical characteristics and the phenotypic attributes of the infused TIL with clinical response. Experimental Design Altogether, 31 transiently lymphodepleted patients were treated with their expanded TIL followed by two cycles of high-dose (HD) IL-2 therapy. The effects of patient clinical features and the phenotypes of the T-cells infused on clinical response were determined. Results Overall, 15/31 (48.4%) patients had an objective clinical response using immune-related response criteria (irRC), with two patients (6.5%) having a complete response. Progression-free survival of >12 months was observed for 9/15 (60%) of the responding patients. Factors significantly associated with objective tumor regression included a higher number of TIL infused, a higher proportion of CD8+ T-cells in the infusion product, a more differentiated effector phenotype of the CD8+ population and a higher frequency of CD8+ T-cells co-expressing the negative costimulation molecule “B- and T-lymphocyte attenuator” (BTLA). No significant difference in telomere lengths of TIL between responders and non-responders was identified. Conclusion These results indicate that immunotherapy with expanded autologous TIL is capable of achieving durable clinical responses in metastatic melanoma patients and that CD8+ T-cells in the infused TIL, particularly differentiated effectors cells and cells expressing BTLA, are associated with tumor regression. PMID:23032743

  15. Predicting Response Trajectories during Cognitive-Behavioural Therapy for Panic Disorder: No Association with the BDNF Gene or Childhood Maltreatment.

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    Martí Santacana

    Full Text Available Anxiety disorders are highly prevalent and result in low quality of life and a high social and economic cost. The efficacy of cognitive-behavioural therapy (CBT for anxiety disorders is well established, but a substantial proportion of patients do not respond to this treatment. Understanding which genetic and environmental factors are responsible for this differential response to treatment is a key step towards "personalized medicine". Based on previous research, our objective was to test whether the BDNF Val66Met polymorphism and/or childhood maltreatment are associated with response trajectories during exposure-based CBT for panic disorder (PD.We used Growth Mixture Modeling to identify latent classes of change (response trajectories in patients with PD (N = 97 who underwent group manualized exposure-based CBT. We conducted logistic regression to investigate the effect on these trajectories of the BDNF Val66Met polymorphism and two different types of childhood maltreatment, abuse and neglect.We identified two response trajectories ("high response" and "low response", and found that they were not significantly associated with either the genetic (BDNF Val66Met polymorphism or childhood trauma-related variables of interest, nor with an interaction between these variables.We found no evidence to support an effect of the BDNF gene or childhood trauma-related variables on CBT outcome in PD. Future studies in this field may benefit from looking at other genotypes or using different (e.g. whole-genome approaches.

  16. Physiological intermolecular modification spectroscopy for the prediction of response to anti-tumor necrosis factor therapy in patients with inflammatory bowel diseases.

    Science.gov (United States)

    Eftekhari, Pierre; Glaubitz, Lisa; Breidert, Matthias; Neurath, Markus Friedrich; Atreya, Raja

    2014-01-01

    Anti-tumor necrosis factor (TNF) antibodies have clinical efficiency only in a subgroup of patients with inflammatory bowel diseases (IBD). Prediction of clinical response is a critical clinical problem. Physiological intermolecular modification spectroscopy (PIMS) is a label-free technology performed in physiological conditions. PIMS enables real-time monitoring of dynamic molecular resonance of entire proteins and macromolecules of an individual. The aim of this study was to explore the capacity of PIMS to discriminate IBD patients regarding response to anti-TNF treatment. Protein extracts of peripheral blood mononuclear cells (PBMC) from 30 outpatients diagnosed with ulcerative colitis (UC) or Crohn's disease (CD) and treated with infliximab were subjected to PIMS analysis in a blinded transversal study. Total protein from each patient's PBMCs was challenged with infliximab. Dynamic changes in macromolecular interaction were registered while the temperature rose from -37 to 37°C. Individual macromolecular volume and molecular elasticity were determined for each patient. Clinical data revealed that 67% of UC and 79% of CD patients responded to infliximab therapy during the 3-month study period based on their respective clinical activity score. These results confirm that PIMS data predicted response to anti-TNF therapy with an accuracy of 96%. PIMS stratified IBD patients into two groups, responders and nonresponders, which correlated with the clinical efficacy of anti-TNF therapy. PIMS seems to be a powerful technology to adapt IBD treatment to the individual patient. Further studies with PIMS might enable to predict clinical response to biological treatment in IBD patients before the therapy is initiated. © 2014 S. Karger AG, Basel.

  17. Changes in thigh muscle volume predict bone mineral density response to lifestyle therapy in frail, obese older adults.

    Science.gov (United States)

    Armamento-Villareal, R; Aguirre, L; Napoli, N; Shah, K; Hilton, T; Sinacore, D R; Qualls, C; Villareal, D T

    2014-02-01

    We studied the relationships among strength, muscle mass, and bone mineral density (BMD) with lifestyle change. Lifestyle therapy consisted of exercise, diet, and diet plus exercise. Diet was by caloric restriction to induce and maintain a weight loss of 10 % from baseline body weight. Exercise attenuated weight loss-induced muscle and bone losses. Exercise improved strength despite muscle loss in patients on diet and exercise. Changes in strength did not correlate with changes in BMD. However, changes in thigh muscle volume correlated with, and predicted changes in hip BMD. Losses of hip BMD and lean body mass are major complications of lifestyle therapy in frail, obese older adults; however, the contribution of mechanical strain loss from muscle loss is poorly defined. We determined the effect of changes in thigh muscle volume and muscle strength on BMD in frail, obese older adults undergoing lifestyle therapy aimed at intentional weight loss with or without exercise. One hundred seven obese older adults were randomized to control, diet, exercise, and diet-exercise groups for 1 year. Thigh muscle volume was measured by magnetic resonance imaging, BMD by DXA, knee strength by dynamometry, total strength by one-repetition maximum (1-RM), and bone markers by immunoassay. Thigh muscle volume decreased in the diet group (-6.2 ± 4.8 %) and increased in the exercise group (2.7 ± 3.1 %), while it was not significantly different from the control in the diet-exercise group. Changes in hip BMD followed similar pattern as those in thigh muscle volume. Knee extension and flexion increased in the exercise group (23 ± 20 %; 25 ± 19 %) and diet-exercise group (20 ± 19 %; 20.6 ± 27 %) but were unchanged in the control and diet groups. Changes in thigh muscle volume correlated with changes in hip BMD (r = 0.55, P = BMD (β = 0.12, P = 0.03) in the multiple regression analyses after accounting for demographic factors and changes in weight and physical activity. There were no

  18. CD8+ T Cells Specific to Apoptosis-Associated Antigens Predict the Response to Tumor Necrosis Factor Inhibitor Therapy in Rheumatoid Arthritis.

    Science.gov (United States)

    Citro, Alessandra; Scrivo, Rossana; Martini, Helene; Martire, Carmela; De Marzio, Paolo; Vestri, Anna Rita; Sidney, John; Sette, Alessandro; Barnaba, Vincenzo; Valesini, Guido

    2015-01-01

    CD8+ T cells specific to caspase-cleaved antigens derived from apoptotic T cells (apoptotic epitopes) represent a principal player in chronic immune activation, which is known to amplify immunopathology in various inflammatory diseases. The purpose of the present study was to investigate the relationship involving these autoreactive T cells, the rheumatoid arthritis immunopathology, and the response to tumor necrosis factor-α inhibitor therapy. The frequency of autoreactive CD8+ T cells specific to various apoptotic epitopes, as detected by both enzyme-linked immunospot assay and dextramers of major histocompatibility complex class I molecules complexed with relevant apoptotic epitopes, was longitudinally analyzed in the peripheral blood of rheumatoid arthritis patients who were submitted to etanercept treatment (or other tumor necrosis factor inhibitors as a control). The percentage of apoptotic epitope-specific CD8+ T cells was significantly higher in rheumatoid arthritis patients than in healthy donors, and correlated with the disease activity. More important, it was significantly more elevated in responders to tumor necrosis factor-α inhibitor therapy than in non-responders before the start of therapy; it significantly dropped only in the former following therapy. These data indicate that apoptotic epitope-specific CD8+ T cells may be involved in rheumatoid arthritis immunopathology through the production of inflammatory cytokines and that they may potentially represent a predictive biomarker of response to tumor necrosis factor-α inhibitor therapy to validate in a larger cohort of patients.

  19. A model to predict pathologic complete response of axillary lymph nodes to neoadjuvant chemo(immuno)therapy in patients with clinically node-positive breast cancer.

    Science.gov (United States)

    Schipper, Robert-Jan; Moossdorff, Martine; Nelemans, Patty J; Nieuwenhuijzen, Grard A P; de Vries, Bart; Strobbe, Luc J A; Roumen, Rudi M H; van den Berkmortel, Franchette; Tjan-Heijnen, Vivianne C G; Beets-Tan, Regina G H; Lobbes, Marc B I; Smidt, Marjolein L

    2014-10-01

    Between 20% and 42% of patients with clinically node-positive breast cancer achieve a pathologic complete response (pCR) of axillary lymph nodes after neoadjuvant chemotherapy or immunotherapy, or both, (chemo[immuno]therapy). Hypothetically, axillary lymph node dissection (ALND) may be safely omitted in these patients. This study aimed to develop a model for predicting axillary pCR in these patients. We retrospectively identified patients with clinically node-positive breast cancer who were treated with neoadjuvant chemo(immuno)therapy and ALND between 2005 and 2012 in 5 hospitals. Patient and tumor characteristics, neoadjuvant chemo(immuno)therapy regimens, and pathology reports were extracted. Binary logistic regression analysis was used to predict axillary pCR with the following variables: age, tumor stage and type, hormone receptor and human epidermal growth factor receptor 2 (HER2) status, and administration of taxane and trastuzumab. The model was internally validated by bootstrap resampling. The overall performance of the model was assessed by the Brier score and the discriminative performance by receiver operating characteristic (ROC) curve analysis. A model was developed based on 291 patients and was internally validated with a scaled Brier score of 0.14. The area under the ROC curve of this model was 0.77 (95% confidence interval [CI], 0.71-0.82). At a cutoff value of predicted probability ≥ 0.50, the model demonstrated specificity of 88%, sensitivity of 43%, positive predictive value (PPV) of 65%, and negative predictive value (NPV) of 75%. This prediction model shows reasonable accuracy for predicting axillary pCR. However, omitting axillary treatment based solely on the nomogram score is not justified. Further research is warranted to noninvasively identify patients with axillary pCR. Copyright © 2014 Elsevier Inc. All rights reserved.

  20. Role of CT Perfusion in Monitoring and Prediction of Response to Therapy of Head and Neck Squamous Cell Carcinoma

    Directory of Open Access Journals (Sweden)

    Lorenzo Preda

    2014-01-01

    Full Text Available This review aims to summarize the technique and clinical applications of CT perfusion (CTp of head and neck cancer. The most common pathologic type (90% of head and neck cancer is squamous cell carcinoma (HNSCC: its diagnostic workup relies on CT and MRI, as they provide an accurate staging for the disease by determining tumour volume, assessing its extension, and detecting of lymph node metastases. Compared with conventional CT and MRI, CTp allows for obtaining measures of tumour vascular physiology and functional behaviour, and it has been demonstrated to be a feasible and useful tool in predicting local outcomes in patients undergoing radiation therapy and chemotherapy and may help monitor both treatments.

  1. A U-shaped type II contraction pattern in patients with strict left bundle branch block predicts super-response to cardiac resynchronization therapy.

    Science.gov (United States)

    Jackson, Tom; Sohal, Manav; Chen, Zhong; Child, Nicholas; Sammut, Eva; Behar, Jonathan; Claridge, Simon; Carr-White, Gerald; Razavi, Reza; Rinaldi, Christopher Aldo

    2014-10-01

    New criteria to define strict left bundle branch block (LBBB) on the basis of pathophysiological principles predict response to cardiac resynchronization therapy (CRT). Heterogeneous activation and contraction patterns have been identified in patients with classical LBBB. Cardiac magnetic resonance (CMR) imaging has demonstrated that a U-shaped (type II) contraction predicts reverse remodeling post-CRT. A homogeneous spread of (type I) contraction is less predictive. The purpose of this study was to investigate contraction patterns among patients with strict LBBB and to test whether a type II contraction pattern better predicts CRT response and super-response. Thirty-seven patients with strict LBBB (QRS duration ≥140 ms for men and ≥130 ms for women with mid-QRS notching or slurring in ≥2 contiguous leads) underwent cine CMR imaging pre-CRT with an analysis of their contraction patterns by using endocardial contour tracking software. Patients were evaluated for reverse remodeling 6 months postimplantation. Nineteen patients (51%) had a type II contraction pattern. A total of 25 patients (68%) of the cohort reverse remodeled. In the type II contraction group, all 19 patients (100%) reverse remodeled as compared with 6 patients (33%) in the type I contraction group (P < .01). Super-response was achieved in 21 patients (57%) of the total cohort: 5 patients with a type I contraction pattern (28%) and 16 patients with a type II contraction pattern (84%) (P < .01). Patients with strict LBBB who are guideline indicated for CRT have heterogeneous contraction patterns derived from cine CMR. A type II contraction pattern is strongly predictive for reverse remodeling and super-response. This questions whether strict LBBB criteria alone are sufficient to reliably predict a positive response to CRT. Copyright © 2014 Heart Rhythm Society. Published by Elsevier Inc. All rights reserved.

  2. Predicting response to cognitive behavioral therapy in contamination-based obsessive-compulsive disorder from functional magnetic resonance imaging.

    Science.gov (United States)

    Olatunji, B O; Ferreira-Garcia, R; Caseras, X; Fullana, M A; Wooderson, S; Speckens, A; Lawrence, N; Giampietro, V; Brammer, M J; Phillips, M L; Fontenelle, L F; Mataix-Cols, D

    2014-07-01

    Although cognitive behavioral therapy (CBT) is an effective treatment for obsessive-compulsive disorder (OCD), few reliable predictors of treatment outcome have been identified. The present study examined the neural correlates of symptom improvement with CBT among OCD patients with predominantly contamination obsessions and washing compulsions, the most common OCD symptom dimension. Participants consisted of 12 OCD patients who underwent symptom provocation with contamination-related images during functional magnetic resonance imaging (fMRI) scanning prior to 12 weeks of CBT. Patterns of brain activity during symptom provocation were correlated with a decrease on the Yale-Brown Obsessive Compulsive Scale (YBOCS) after treatment, even when controlling for baseline scores on the YBOCS and the Beck Depression Inventory (BDI) and improvement on the BDI during treatment. Specifically, activation in brain regions involved in emotional processing, such as the anterior temporal pole and amygdala, was most strongly associated with better treatment response. By contrast, activity in areas involved in emotion regulation, such as the dorsolateral prefrontal cortex, correlated negatively with treatment response mainly in the later stages within each block of exposure during symptom provocation. Successful recruitment of limbic regions during exposure to threat cues in patients with contamination-based OCD may facilitate a better response to CBT, whereas excessive activation of dorsolateral prefrontal regions involved in cognitive control may hinder response to treatment. The theoretical implications of the findings and their potential relevance to personalized care approaches are discussed.

  3. Efficacy of LOw-dose DObutamine stress-echocardiography to predict cardiac resynchronization therapy response (LODO-CRT) multicenter prospective study: design and rationale.

    Science.gov (United States)

    Muto, Carmine; Gasparini, Maurizio; Iacopino, Saverio; Peraldo, Carlo; Curnis, Antonio; Sassone, Biagio; Diotallevi, Paolo; Davinelli, Mario; Valsecchi, Sergio; Tuccillo, Bernardino

    2008-10-01

    Although cardiac resynchronization therapy (CRT) has a well-demonstrated therapeutic effect in selected patients with advanced heart failure on optimized drug therapy, nonresponder rate remains high. The LODO-CRT is designed to improve patient selection for CRT. Design and rationale of this study are presented herein. LODO-CRT is a multicenter prospective study, started in late 2006, that enrolls patients with conventional indications for CRT (symptomatic stable New York Heart Association class III-IV on optimized drug therapy, QRS > or =120 milliseconds, left ventricular [LV] dilatation, LV ejection fraction 5 units), in predicting CRT response during follow-up. Assessment of CRT effects will follow 2 sequential phases: in phase 1, CRT response end point is defined as LV end-systolic volume reduction > or =10% at 6 months; in phase 2, both LV end-systolic volume reduction and clinical status via a clinical composite score will be evaluated at 12 months follow-up. Predictive value of LVCR will be compared to other measures, such as LV dyssynchrony measures, through adjusted multivariable analysis. For the purpose of the study, target patient number is 270 (with 95% confidence, 80% power, alpha LODO-CRT trial is testing the hypothesis that LVCR assessment, using low-dose dobutamine stress echocardiography test, should effectively predict positive response to CRT both in terms of the reverse remodeling process as well as favorable long-term clinical outcome. Moreover, the predictive value of LVCR will be compared to that of conventional intra-LV dyssynchrony measures.

  4. Regulatory T cell frequency, but not plasma IL-33 levels, represents potential immunological biomarker to predict clinical response to intravenous immunoglobulin therapy.

    Science.gov (United States)

    Maddur, Mohan S; Stephen-Victor, Emmanuel; Das, Mrinmoy; Prakhar, Praveen; Sharma, Varun K; Singh, Vikas; Rabin, Magalie; Trinath, Jamma; Balaji, Kithiganahalli N; Bolgert, Francis; Vallat, Jean-Michel; Magy, Laurent; Kaveri, Srini V; Bayry, Jagadeesh

    2017-03-20

    Intravenous immunoglobulin (IVIG) is a polyspecific pooled immunoglobulin G preparation and one of the commonly used therapeutics for autoimmune diseases including those of neurological origin. A recent report in murine model proposed that IVIG expands regulatory T (Treg) cells via induction of interleukin 33 (IL-33). However, translational insight on these observations is lacking. Ten newly diagnosed Guillain-Barré syndrome (GBS) patients were treated with IVIG at the rate of 0.4 g/kg for three to five consecutive days. Clinical evaluation for muscular weakness was performed by Medical Research Council (MRC) and modified Rankin scoring (MRS) system. Heparinized blood samples were collected before and 1, 2, and 4-5 weeks post-IVIG therapy. Peripheral blood mononuclear cells were stained for surface CD4 and intracellular Foxp3, IFN-γ, and tumor necrosis factor alpha (TNF-α) and were analyzed by flow cytometry. IL-33 and prostaglandin E2 in the plasma were measured by ELISA. The fold changes in plasma IL-33 at week 1 showed no correlation with the MRC and MRS scores at weeks 1, 2, and ≥4 post-IVIG therapy. Clinical recovery following IVIG therapy appears to be associated with Treg cell response. Contrary to murine study, there was no association between the fold changes in IL-33 at week 1 and Treg cell frequency at weeks 1, 2, and ≥4 post-IVIG therapy. Treg cell-mediated clinical response to IVIG therapy in GBS patients was associated with reciprocal regulation of effector T cells-expressing TNF-α. Treg cell expansion by IVIG in patients with autoimmune diseases lack correlation with IL-33. Treg cell frequency, but not plasma IL-33 levels, represents potential immunological biomarker to predict clinical response to IVIG therapy.

  5. Prediction of Treatment Response at 5-year Follow-up in a Randomized Clinical Trial of Behaviorally Based Couple Therapies

    Science.gov (United States)

    Baucom, Brian R.; Atkins, David C.; Rowe, Lorelei Simpson; Doss, Brian D.; Christensen, Andrew

    2014-01-01

    Objective Building on earlier work examining predictors of short- and moderate-term treatment response, demographic, intrapersonal, communication, and interpersonal variables were examined as predictors of clinically significant outcomes five years after couples completed one of two behaviorally based couple therapies. Method One hundred and thirty-four couples were randomly assigned to Integrative Behavioral Couple Therapy (IBCT; Jacobson & Christensen, 1998) or Traditional Behavioral Couple Therapy (TBCT; Jacobson & Margolin, 1979) and followed for 5 years after treatment. Outcomes include clinically significant change categories of relationship satisfaction and marital status at 5-year follow-up. Optimal subsets of predictors were selected using an automated, bootstrapped selection procedure based on Bayesian Information Criterion. Results Higher levels of commitment and being married for a longer period of time were associated with decreased likelihood of divorce/separation (Odds Ratio [OR] = 1.39, p = .004; OR = 0.91, p = .015). Being married for a longer period of time was also associated with increased likelihood of positive, clinically significant change (OR = 1.12, p = .029). Finally, higher levels of wife desired closeness were associated with increased odds of positive, clinically significant change and decreased odds of divorce for moderately distressed, IBCT couples (OR = 1.16, p = 0.002; OR = 0.85, p = 0.007, respectively) whereas the opposite was true for moderately distressed, TBCT couples (OR = 0.77, p divorced and most likely to report improvements in relationship satisfaction five years after ending treatment. In addition, it appears that the impact of wives’ desired closeness depended on the type of treatment moderately distressed couple received. PMID:25265544

  6. Prediction of treatment response at 5-year follow-up in a randomized clinical trial of behaviorally based couple therapies.

    Science.gov (United States)

    Baucom, Brian R; Atkins, David C; Rowe, Lorelei Simpson; Doss, Brian D; Christensen, Andrew

    2015-02-01

    Building on earlier work examining predictors of short- and moderate-term treatment response, demographic, intrapersonal, communication, and interpersonal variables were examined as predictors of clinically significant outcomes 5 years after couples completed 1 of 2 behaviorally based couple therapies. One hundred and thirty-four couples were randomly assigned to Integrative Behavioral Couple Therapy (IBCT; Jacobson & Christensen, 1998) or Traditional Behavioral Couple Therapy (TBCT; Jacobson & Margolin, 1979) and followed for 5 years after treatment. Outcomes include clinically significant change categories of relationship satisfaction and marital status at 5-year follow-up. Optimal subsets of predictors were selected using an automated, bootstrapped selection procedure based on Bayesian information criterion. Higher levels of commitment and being married for a longer period of time were associated with decreased likelihood of divorce or separation (odds ratio [OR] = 1.39, p = .004; OR = 0.91, p = .015). Being married for a longer period of time was also associated with increased likelihood of positive, clinically significant change (OR = 1.12, p = .029). Finally, higher levels of wife-desired closeness were associated with increased odds of positive, clinically significant change and decreased odds of divorce for moderately distressed, IBCT couples (OR = 1.16, p = .002; OR = 0.85, p = .007, respectively), whereas the opposite was true for moderately distressed, TBCT couples (OR = 0.77, p < .001; OR = 1.17, p = .002, respectively). Commitment-related variables are associated with clinically significant outcomes at 5-year follow-up as well as at termination and moderate-term follow-up. (PsycINFO Database Record (c) 2015 APA, all rights reserved).

  7. Clinical application of a systems model of apoptosis execution for the prediction of colorectal cancer therapy responses and personalisation of therapy

    LENUS (Irish Health Repository)

    Hector, S.

    2012-06-15

    Objective Key to the clinical management of colorectal cancer is identifying tools which aid in assessing patient prognosis and determining more effective and personalised treatment strategies. We evaluated whether an experimental systems biology strategy which analyses the susceptibility of cancer cells to undergo caspase activation can be exploited to predict patient responses to 5-fluorouracil-based chemotherapy and to case-specifically identify potential alternative targeted treatments to reactivate apoptosis. \\r\

  8. Early survival prediction after intra-arterial therapies: a 3D quantitative MRI assessment of tumour response after TACE or radioembolization of colorectal cancer metastases to the liver

    Energy Technology Data Exchange (ETDEWEB)

    Chapiro, Julius; Savic, Lynn Jeanette [The Johns Hopkins Hospital, Russell H. Morgan Department of Radiology and Radiological Science, Division of Vascular and Interventional Radiology, Baltimore, MD (United States); Charite Universitaetsmedizin, Department of Diagnostic and Interventional Radiology, Berlin (Germany); Duran, Rafael; Schernthaner, Ruediger; Wang, Zhijun; Geschwind, Jean-Francois [The Johns Hopkins Hospital, Russell H. Morgan Department of Radiology and Radiological Science, Division of Vascular and Interventional Radiology, Baltimore, MD (United States); Lin, MingDe [The Johns Hopkins Hospital, Russell H. Morgan Department of Radiology and Radiological Science, Division of Vascular and Interventional Radiology, Baltimore, MD (United States); U/S Imaging and Interventions (UII), Philips Research North America, Briarcliff Manor, NY (United States); Lesage, David [Philips Research, Medisys, Suresnes (France)

    2015-07-15

    This study evaluated the predictive role of 1D, 2D and 3D quantitative, enhancement-based MRI regarding overall survival (OS) in patients with colorectal liver metastases (CLM) following intra-arterial therapies (IAT). This retrospective analysis included 29 patients who underwent transarterial chemoembolization (TACE) or radioembolization and received MRI within 6 weeks after therapy. Tumour response was assessed using 1D and 2D criteria (such as European Association for the Study of the Liver guidelines [EASL] and modified Response Evaluation Criteria in Solid Tumors [mRECIST]). In addition, a segmentation-based 3D quantification of overall (volumetric [v] RECIST) and enhancing lesion volume (quantitative [q] EASL) was performed on portal venous phase MRI. Accordingly, patients were classified as responders (R) and non-responders (NR). Survival was evaluated using Kaplan-Meier analysis and compared using Cox proportional hazard ratios (HR). Only enhancement-based criteria identified patients as responders. EASL and mRECIST did not predict patient survival (P = 0.27 and P = 0.44, respectively). Using uni- and multivariate analysis, qEASL was identified as the sole predictor of patient survival (9.9 months for R, 6.9 months for NR; P = 0.038; HR 0.4). The ability of qEASL to predict survival early after IAT provides evidence for potential advantages of 3D quantitative tumour analysis. (orig.)

  9. Strong anti-Epstein Barr virus (EBV) or cytomegalovirus (CMV) cellular immune responses predict survival and a favourable response to anti-tuberculosis therapy.

    Science.gov (United States)

    Nagu, Tumaini; Aboud, Said; Rao, Martin; Matee, Mecky; Axelsson, Rebecca; Valentini, Davide; Mugusi, Ferdinand; Zumla, Alimuddin; Maeurer, Markus

    2017-03-01

    Intact immune responses to cytomegalovirus (CMV) and Epstein-Barr virus (EBV) represent a biologically and clinically relevant correlate of 'immunological fitness' in humans. However, there is a lack of knowledge concerning anti-EBV or anti-CMV responses in patients with pulmonary tuberculosis (TB), in whom aberrant immune responses may promote progression of clinical disease. Venous blood samples were obtained at the time of (sputum smear positive) pulmonary TB diagnosis. A whole blood assay was performed by exposing PBMCs (peripheral blood mononuclear cells) to a panel of infectious antigens, including CMV, EBV and mycobacterial proteins. Cell culture supernatants were collected after seven days and interferon gamma (IFN-γ) was measured using a sandwich ELISA. Patients received standard first line anti-tuberculosis rifampicin (R)/isoniazid (H)/ethambutol (E)/pyrazinamide (Z) for two months followed by RH for four months. PBMCs from cured patients (after treatment completion) exhibited significantly stronger IFN-γ responses to CMV (p=0.035), EBV (p=0.006) or Mycobacterium tuberculosis ESAT-6 (p=0.043) at the time of diagnosis as compared to patients who succumbed to TB during treatment. IFN-γ responses to other viral (H5N1, HSV-1) as well as other mycobacterial (Ag85A, Rv2958c, Rv0447c) antigens were not found to be significantly different among patients who were cured or those who succumbed to TB. Increased cellular immune responses to CMV and EBV antigens at the time of diagnosis of pulmonary tuberculosis are associated with increased survival after a standard six months anti-TB therapy. CVM and EBV antigens may represent "intrinsic markers for immune fitness" and guide improved TB therapies including host-directed therapies. Copyright © 2017. Published by Elsevier Ltd.

  10. Music Therapy and Music Therapy Research. Response

    DEFF Research Database (Denmark)

    Pedersen, Inge Nygaard

    2002-01-01

    This response to Keynote by Prof. Even Ruud (N)"Music Education and Music Therapy seeks to define these two areas with specific focus on tools and methods for analysis of music as these methods are developed in music therapy. This includes that the music therapist, the music and the client create...

  11. Sodium (18)F-sodium fluoride PET failed to predict responses to TNFα antagonist therapy in 31 patients with possible spondyloarthritis not meeting ASAS criteria.

    Science.gov (United States)

    Darrieutort-Laffite, Christelle; Ansquer, Catherine; Maugars, Yves; Le Goff, Benoît; Bodere, Françoise; Berthelot, Jean-Marie

    2015-12-01

    To determine whether (18)F-NaF positron-emission tomography (PET) contributes to the diagnosis of spondyloarthritis and whether observed uptakes predict the response to TNFα antagonist therapy. We studied patients who had suspected spondyloarthritis but did not meet ASAS criteria and who were referred for an assessment of eligibility for TNFα antagonist therapy. (18)F-NaF PET was offered instead of bone scintigraphy. TNFα antagonist therapy was given if the clinician's level of confidence in the diagnosis of spondyloarthritis based on (18)F-NaF PET findings was ≥50/100. Thirty-one patients accepted to undergo (18)F-NaF PET. Their mean age was 39.9±11.7 years; 22% were HLA-B27-positive and none had evidence of sacroiliitis by magnetic resonance imaging. Of the 31 patients, 30 had abnormal (18)F-NaF PET findings. However, of the 312 high-uptake foci, only 123 (39.4%) matched sites of pain. TNFα antagonist therapy was given to 16 patients. The treated group and untreated group (n=15) were not significantly different for the mean number of high-uptake foci per patient (11.7±8.1 vs. 8.3±5.1, respectively) or for the proportion of patients with high uptake by the sacroiliac joints (13/16 [81%] vs. 8/15 [53%], respectively). In the treated group, 5 patients met ASAS response criteria after 3 months. These 5 patients were among the 9 treated patients who met Amor's modified criteria (arthritis instead of asymmetrical oligoarthritis). In the 5 responders, the (18)F-NaF uptake scores were nonsignificantly lower than in the 11 nonresponders (9.0±8.5 vs. 13.0±6.4, respectively). In the patients for whom the (18)F-NaF PET findings increased the level of confidence in the diagnosis of spondyloarthritis, this effect was short-lived. The positive predictive value of (18)F-NaF PET for diagnosing spondyloarthritis or predicting a response to TNFα antagonist therapy seems very low. This finding is probably ascribable to poor specificity. Copyright © 2015 Société fran

  12. TERT promoter mutations contribute to IDH mutations in predicting differential responses to adjuvant therapies in WHO grade II and III diffuse gliomas.

    Science.gov (United States)

    Zhang, Zhen-Yu; Chan, Aden Ka-Yin; Ding, Xiao-Jie; Qin, Zhi-Yong; Hong, Christopher S; Chen, Ling-Chao; Zhang, Xin; Zhao, Fang-Ping; Wang, Yin; Wang, Yang; Zhou, Liang-Fu; Zhuang, Zhengping; Ng, Ho-Keung; Yan, Hai; Yao, Yu; Mao, Ying

    2015-09-22

    IDH mutations frequently occur in WHO grade II and III diffuse gliomas and have favorable prognosis compared to wild-type tumors. However, whether IDH mutations in WHO grade II and II diffuse gliomas predict enhanced sensitivity to adjuvant radiation (RT) or chemotherapy (CHT) is still being debated. Recent studies have identified recurrent mutations in the promoter region of telomerase reverse transcriptase (TERT) in gliomas. We previously demonstrated that TERT promoter mutations may be promising biomarkers in glioma survival prognostication when combined with IDH mutations. This study analyzed IDH and TERT promoter mutations in 295 WHO grade II and III diffuse gliomas treated with or without adjuvant therapies to explore their impact on the sensitivity of tumors to genotoxic therapies. IDH mutations were found in 216 (73.2%) patients and TERT promoter mutations were found in 112 (38%) patients. In multivariate analysis, IDH mutations (p IDH and TERT promoter mutations were not significant prognostic factors in patients who did not receive genotoxic therapies. Adjuvant RT and CHT were factors independently impacting PFS (RT p = 0.001, CHT p = 0.026) in IDH mutated WHO grade II and III diffuse gliomas but not in IDH wild-type group. Univariate and multivariate analyses demonstrated TERT promoter mutations further stratified IDH wild-type WHO grade II and III diffuse gliomas into two subgroups with different responses to genotoxic therapies. Adjuvant RT and CHT were significant parameters influencing PFS in the IDH wt/TERT mut subgroup (RT p = 0.015, CHT p = 0.015) but not in the IDH wt/TERT wt subgroup. Our data demonstrated that IDH mutated WHO grade II and III diffuse gliomas had better PFS and OS than their IDH wild-type counterparts when genotoxic therapies were administered after surgery. Importantly, we also found that TERT promoter mutations further stratify IDH wild-type WHO grade II and III diffuse gliomas into two subgroups with different responses to

  13. Neither Baseline nor Changes in Serum Triiodothyronine during Levothyroxine/Liothyronine Combination Therapy Predict a Positive Response to This Treatment Modality in Hypothyroid Patients with Persistent Symptoms.

    Science.gov (United States)

    Medici, Bjarke Borregaard; la Cour, Jeppe Lerche; Michaelsson, Luba Freja; Faber, Jens Oscar; Nygaard, Birte

    2017-04-01

    Despite biochemical euthyroidism, some levothyroxine (L-T4)-treated hypothyroid patients report persisting symptoms and some of these patients are tentatively treated with a combination of L-T4 and liothyronine (L-T3). Combination therapy and the appropriate choice of blood tests to monitor treatment are highly debated among specialists and patients. To evaluate whether measuring serum triiodothyronine (S-T3) at baseline or during combination therapy can be used as an indicator of a positive effect from L-T4/L-T3 combination therapy. Observational retrospective study of patients (n = 42) with persisting symptoms of hypothyroidism despite L-T4 therapy who had normal TSH levels and did not have any comorbidities that could explain their symptoms. All were then treated with L-T4/L-T3 combination therapy at a dose ratio of 17/1 according to European Thyroid Association guidelines. Based on patient-reported outcome, they were divided into responders and nonresponders. Five patients were lost to follow-up and thus excluded. At the 3-month follow-up, 11 were classified as nonresponders and 26 as responders. At 12 months these figures had changed to 13 (35%) and 24 (65%), respectively. When comparing responders versus nonresponders, no differences were seen at baseline or during follow-up in S-T3 and in free T3 estimates. Further, logistic regression showed no correlation between S-T3 and free T3 estimates and responder/nonresponder status. Our data indicate that serum T3 measurements are not suitable to predict which patient will benefit from L-T4/L-T3 combination therapy, and treatment response cannot be followed by repeated T3 measurements either.

  14. Analyses of Potential Predictive Markers and Response to Targeted Therapy in Patients with Advanced Clear-cell Renal Cell Carcinoma

    Directory of Open Access Journals (Sweden)

    Yan Song

    2015-01-01

    Full Text Available Background: Vascular endothelial growth factor-targeted agents are standard treatments in advanced clear-cell renal cell carcinoma (ccRCC, but biomarkers of activity are lacking. The aim of this study was to investigate the association of Von Hippel-Lindau (VHL gene status, vascular endothelial growth factor receptor (VEGFR or stem cell factor receptor (KIT expression, and their relationships with characteristics and clinical outcome of advanced ccRCC. Methods: A total of 59 patients who received targeted treatment with sunitinib or pazopanib were evaluated for determination at Cancer Hospital and Institute, Chinese Academy of Medical Sciences between January 2010 and November 2012. Paraffin-embedded tumor samples were collected and status of the VHL gene and expression of VEGFR and KIT were determined by VHL sequence analysis and immunohistochemistry. Clinical-pathological features were collected and efficacy such as response rate and Median progression-free survival (PFS and overall survival (OS were calculated and then compared based on expression status. The Chi-square test, the Kaplan-Meier method, and the Lon-rank test were used for statistical analyses. Results: Of 59 patients, objective responses were observed in 28 patients (47.5%. The median PFS was 13.8 months and median OS was 39.9 months. There was an improved PFS in patients with the following clinical features: Male gender, number of metastatic sites 2 or less, VEGFR-2 positive or KIT positive. Eleven patients (18.6% had evidence of VHL mutation, with an objective response rate of 45.5%, which showed no difference with patients with no VHL mutation (47.9%. VHL mutation status did not correlate with either overall response rate (P = 0.938 or PFS (P = 0.277. The PFS was 17.6 months and 22.2 months in VEGFR-2 positive patients and KIT positive patients, respectively, which was significantly longer than that of VEGFR-2 or KIT negative patients (P = 0.026 and P = 0.043. Conclusion

  15. Brain-behavioral adaptability predicts response to cognitive behavioral therapy for emotional disorders: A person-centered event-related potential study.

    Science.gov (United States)

    Stange, Jonathan P; MacNamara, Annmarie; Kennedy, Amy E; Hajcak, Greg; Phan, K Luan; Klumpp, Heide

    2017-06-23

    Single-trial-level analyses afford the ability to link neural indices of elaborative attention (such as the late positive potential [LPP], an event-related potential) with downstream markers of attentional processing (such as reaction time [RT]). This approach can provide useful information about individual differences in information processing, such as the ability to adapt behavior based on attentional demands ("brain-behavioral adaptability"). Anxiety and depression are associated with maladaptive information processing implicating aberrant cognition-emotion interactions, but whether brain-behavioral adaptability predicts response to psychotherapy is not known. We used a novel person-centered, trial-level analysis approach to link neural indices of stimulus processing to behavioral responses and to predict treatment outcome. Thirty-nine patients with anxiety and/or depression received 12 weeks of cognitive behavioral therapy (CBT). Prior to treatment, patients performed a speeded reaction-time task involving briefly-presented pairs of aversive and neutral pictures while electroencephalography was recorded. Multilevel modeling demonstrated that larger LPPs predicted slower responses on subsequent trials, suggesting that increased attention to the task-irrelevant nature of pictures interfered with reaction time on subsequent trials. Whereas using LPP and RT averages did not distinguish CBT responders from nonresponders, in trial-level analyses individuals who demonstrated greater ability to benefit behaviorally (i.e., faster RT) from smaller LPPs on the previous trial (greater brain-behavioral adaptability) were more likely to respond to treatment and showed greater improvements in depressive symptoms. These results highlight the utility of trial-level analyses to elucidate variability in within-subjects, brain-behavioral attentional coupling in the context of emotion processing, in predicting response to CBT for emotional disorders. Copyright © 2017 Elsevier Ltd

  16. Early biomarkers from dynamic contrast-enhanced magnetic resonance imaging to predict the response to antiangiogenic therapy in high-grade gliomas

    Energy Technology Data Exchange (ETDEWEB)

    Piludu, Francesca; Vidiri, Antonello [Regina Elena National Cancer Institute, Radiology and Diagnostic Imaging Department, Rome (Italy); Marzi, Simona [Regina Elena National Cancer Institute, Medical Physics Laboratory, Rome (Italy); Pace, Andrea; Villani, Veronica [Regina Elena National Cancer Institute, Neurology Division, Rome (Italy); Fabi, Alessandra [Regina Elena National Cancer Institute, Oncology Department, Rome (Italy); Carapella, Carmine Maria [Regina Elena National Cancer Institute, Oncologic Surgery Department, Rome (Italy); Terrenato, Irene [Regina Elena National Cancer Institute, Biostatistics-Scientific Direction, Rome (Italy); Antenucci, Anna [Regina Elena National Cancer Institute, Clinical Pathology, Rome (Italy)

    2015-12-15

    The aim of this study is to investigate whether early changes in tumor volume and perfusion measurements derived from dynamic contrast-enhanced magnetic resonance imaging (DCE-MRI) may predict response to antiangiogenic therapy in recurrent high-grade gliomas. Twenty-seven patients who received bevacizumab every 3 weeks were enrolled in the study. For each patient, three MRI scans were performed: at baseline, after the first dose, and after the fourth dose of bevacizumab. The entire tumor volume (V{sub tot}), as well as contrast-enhanced and noncontrast-enhanced tumor subvolumes (V{sub CE-T1} and V{sub NON-CE-T1}, respectively) were outlined using post-contrast T1-weighted images as a guide for the tumor location. Histogram analysis of normalized IAUGC (nIAUGC) and transfer constant K{sup trans} maps were performed. Each patient was classified as a responder patient if he/she had a partial response or a stable disease or as a nonresponder patient if he/she had progressive disease. Responding patients showed a larger reduction in V{sub NON-CE-T1} after a single dose, compared to nonresponding patients. Tumor subvolumes with increased values of nIAUGC and K{sup trans}, after a single dose, significantly differed between responders and nonresponders. The radiological response was found to be significantly associated to the clinical outcome. After a single dose, V{sub tot} was predictive of overall survival (OS), while V{sub CE-T1} showed a tendency of correlation with OS. Tumor subvolumes with increased nIAUGC and K{sup trans} showed the potential for improving the diagnostic accuracy of DCE. Early assessments of the entire tumor volume, including necrotic areas, may provide complementary information of tumor behavior in response to anti-VEGF therapies and is worth further investigation. (orig.)

  17. Prediction of flap response.

    Science.gov (United States)

    Potgieter, Frederik J; Roberts, Cynthia; Cox, Ian G; Mahmoud, Ashraf M; Herderick, Edward E; Roetz, Marlize; Steenkamp, Wouter

    2005-01-01

    To find predictors of the induced biomechanical and optical effects of lamellar flap creation on the cornea. Optimed Eye and Laser Clinic, Pretoria, South Africa, and the Department of Ophthalmology and Biomedical Engineering Center, The Ohio State University, Columbus, Ohio, and Bausch & Lomb Vision Research Laboratory, Rochester, New York, USA. This prospective study monitored the refractive, wavefront aberration, and corneal topographic changes in 29 eyes of 15 patients for 3 months after the creation of a corneal lamellar flap. The main outcome measures for statistical analysis were refraction, total corneal thickness, residual corneal bed thickness, horizontal white-to-white corneal diameter, horizontal flap diameter, topography data, and wavefront data. Statistically significant changes were seen in the autorefraction mode. Wavefront data showed significant change in 4 Zernike modes-90/180-degree astigmatism, vertical coma, horizontal coma, and spherical aberration. The topography data indicated the corneal biomechanical response was significantly predicted by stromal bed thickness in the early follow-up period and by total corneal pachymetry and flap diameter in a 2-parameter statistical model in the late follow-up period. Uncomplicated lamellar flap creation is responsible for systematic changes in corneal topography and induction of higher-order optical aberrations. Predictors of this response include stromal bed thickness, flap diameter, and total corneal pachymetry.

  18. Prediction of a good response to cardiac resynchronization therapy in patients with severe dilated cardyomyopathy: could conventional echocardiography be the answer after all?

    Science.gov (United States)

    Petrovic, Milan; Petrovic, Marija T; Milasinovic, Goran; Vujisic-Tesic, Bosiljka; Trifunovic, Danijela; Nedeljkovic, Ivana; Calovic, Zarko; Ivanovic, Branislava; Tesic, Milorad; Boricic, Marija; Petrovic, Olga; Petrovic, Ivana M; Banovic, Marko; Draganic, Gordana; Ostojic, Miodrag

    2012-03-01

    The aim of this study was to assess the performance of echocardiographic parameters to predict response to cardiac resynchronization therapy (CRT). CRT reduces morbidity and mortality due to the proper selection of candidates for CRT. The 12-month trial was performed on 70 optimally medicated patients with standard inclusion criteria: NYHA class III or IV heart failure, left ventricular ejection fraction (LVEF) ≤ 35%, and QRS ≥ 120 ms. All parameters were evaluated by conventional and tissue Doppler-based methods. Indicator of positive CRT response was more than 20% in improvement of LVEF. LVEF increased >20% in 42 patients. Out of 43 tested baseline echocardiographic parameters, 12 showed statistical difference between responders and nonresponders. Out of these 12 parameters, six (LVSV, LVSI, LVFS, RVd, VPMR, and PISA) had modest to moderately good ability to predict LVEF response with sensitivity ranging from 62.2% to 82.4%, and specificity ranging from 56.5% to 81.2%. For those parameters, the area under the receiver-operating characteristic curve for positive response to CRT was ≤0.76. Multivariate regression analysis resulted in selection of LVSI and LVFS as possible predictive independent parameters for a good response. The cutoff value for LVSI was 38.7 mL/m(2) (P = 0.045) and for LVFS was 13% (P = 0.032). Contribution of LVSI and LVFS is to be confirmed in larger trials. Simplicity of their assessment by conventional echocardiography could be an argument for adding them to the inclusion criteria for CRT in severe heart failure patients. © 2011, Wiley Periodicals, Inc.

  19. Sequential FDG-PET/CT reliably predicts response of locally advanced rectal cancer to neo-adjuvant chemo-radiation therapy

    Energy Technology Data Exchange (ETDEWEB)

    Capirci, Carlo [Hospital, Division of Radiotherapy, Rovigo (Italy); Rampin, Lucia; Banti, Elena [Hospital, Nuclear Medicine and PET Service, Rovigo (Italy); Erba, Paola A.; Mariani, Giuliano [Regional Center of Nuclear Medicine, Univ. Pisa (Italy); Galeotti, Fabrizio [Hospital, Division of Surgery, Rovigo (Italy); Crepaldi, Giorgio [Hospital, Division of Oncology, Rovigo (Italy); Gava, Marcello [Hospital, Medical Physics Service, Rovigo (Italy); Fanti, Stefano [Politecnico Bologna (Italy). Dept. of Nuclear Medicine; Muzzio, Pier C. [Dept. of Radiology, Ist. Oncologico, Padova (Italy); Rubello, Domenico [Rovigo Hospital, Istituto Oncologico Veneto (IOV)-IRCCS, Nuclear Medicine Service, PET Unit, Rovigo (Italy)

    2007-10-15

    Prediction of rectal cancer response to preoperative, neo-adjuvant chemo-radiation therapy (CRT) provides the opportunity to identify patients in whom a major response is expected and who may therefore benefit from alternative surgical approaches. Traditional morphological imaging techniques are effective in defining tumour extension in the initial diagnostic and staging work-up, but perform poorly in distinguishing residual neoplastic tissue from scarring post CRT, when restaging the patient before surgery. Fluorine-18 fluorodeoxyglucose positron emission tomography (FDG-PET) is a promising tool for monitoring the effect of anti-tumour therapy. The aim of this study was to prospectively assess the value of sequential FDG-PET scans in predicting the response of locally advanced rectal cancer to neo-adjuvant CRT. Forty-four consecutive patients with locally advanced (cT3-4) primary rectal cancer and four patients with pelvic recurrence of rectal cancer were enrolled in this prospective study. Treatment consisted of external beam intensified radiotherapy, chemotherapy and, 8-10 weeks later, surgery with curative intent. All patients underwent FDG-PET/CT both before CRT and 5-6 weeks after completing CRT. One patient died before surgery because of acute myocardial infarction, and was therefore excluded from further analysis. Semi-quantitative measurements of FDG uptake (SUV{sub max}), absolute difference ({delta}SUV{sub max}) and percent SUV{sub max} difference (Response Index, RI) between pre- and post-CRT PET scans were considered. Results were correlated with pathological response, assessed both by histopathological staging of the surgical specimens (pTNM) and by the tumour regression grade (TRG) according to Mandard's criteria (patients with TRG1-2 being defined as responders and patients with TRG3-5 as non-responders). Following neo-adjuvant CRT, of the 45 patients submitted to surgery, 23 (51.1%) were classified as responders according to Mandard

  20. Assessing Imaging Response to Therapy.

    Science.gov (United States)

    Minocha, Jeet; Lewandowski, Robert J

    2015-09-01

    Locoregional therapies (LRTs) have proved valuable in the treatment of patients with cancer, most commonly in the liver. Accurate assessment of response to these therapies is crucial because objective response can be a surrogate of improved survival. Imaging plays an essential role in the objective evaluation of tumor response to most cancer therapies, including LRTs. Assessing imaging response to LRTs, however, can be challenging and is evolving. This article reviews the different criteria used to assess radiologic response to LRTs, with special attention to imaging assessment following treatment of hepatocellular carcinoma. Copyright © 2015 Elsevier Inc. All rights reserved.

  1. PET imaging-based phenotyping as a predictive biomarker of response to tyrosine kinase inhibitor therapy in non-small cell lung cancer: Are we there yet?

    Energy Technology Data Exchange (ETDEWEB)

    Gerbaudo, Victor H.; Kim, Chun K. [Div. of Nuclear Medicine and Molecular Imaging, Dept. of Radiology,Brigham and Women' s Hospital and Harvard Medical School, Boston (United States)

    2017-03-15

    The increased understanding of the molecular pathology of different malignancies, especially lung cancer, has directed investigational efforts to center on the identification of different molecular targets and on the development of targeted therapies against these targets. A good representative is the epidermal growth factor receptor (EGFR); a major driver of non-small cell lung cancer tumorigenesis. Today, tumor growth inhibition is possible after treating lung tumors expressing somatic mutations of the EGFR gene with tyrosine kinase inhibitors (TKI). This opened the doors to biomarker-directed precision or personalized treatments for lung cancer patients. The success of these targeted anticancer therapies depends in part on being able to identify biomarkers and their patho-molecular make-up in order to select patients that could respond to specific therapeutic agents. While the identification of reliable biomarkers is crucial to predict response to treatment before it begins, it is also essential to be able to monitor treatment early during therapy to avoid the toxicity and morbidity of futile treatment in non-responding patients. In this context, we share our perspective on the role of PET imaging-based phenotyping in the personalized care of lung cancer patients to non-invasively direct and monitor the treatment efficacy of TKIs in clinical practice.

  2. Low-dose dobutamine stress echocardiography to assess left ventricular contractile reserve for cardiac resynchronization therapy: data from the Low-Dose Dobutamine Stress Echocardiography to Predict Cardiac Resynchronization Therapy Response (LODO-CRT) trial.

    Science.gov (United States)

    Iacopino, Saverio; Gasparini, Maurizio; Zanon, Francesco; Dicandia, Cosimo; Distefano, Giuseppe; Curnis, Antonio; Donati, Roberto; Neja, Carlo P; Calvi, Valeria; Davinelli, Mario; Novelli, Vanessa; Muto, Carmine

    2010-01-01

    Cardiac resynchronization therapy (CRT) is an effective methodology indicated in selected heart failure patients. Identifying responders to the therapy is still challenging. Most studies report that at least 30% of the patients are nonresponders. Baseline characteristics of the Low-Dose Dobutamine Stress Echocardiography to Predict Cardiac Resynchronization Therapy Response (LODO-CRT) trial population are presented. The study investigates dobutamine stress echocardiography's role in predicting CRT response. Two hundred seventy-one CRT candidates were studied. Mean age was 67+/-10 years, 69% were male, 96% had New York Heart Association class III disease, and 39% had heart failure of ischemic etiology. Mean QRS and left ventricular ejection fraction were 146+/-24 ms and 26%+/-6%, respectively. Seventy-seven percent of participants showed contractile reserve. Left ventricular end-diastolic volume was shown to be independently associated with contractile reserve presence. In particular, more dilated ventricles are associated with a lower chance of having contractile reserve. The LODO-CRT trial enrolled a cohort of patients fulfilling criteria for CRT. Dobutamine stress echocardiography was highly feasible and safe in this population. Contractile reserve was associated with healthier ventricles. (c) 2010 Wiley Periodicals, Inc.

  3. Lowering of proteinuria in response to antihypertensive therapy predicts improved renal function in late but not in early diabetic nephropathy: a pooled analysis.

    Science.gov (United States)

    Jerums, George; Panagiotopoulos, Sianna; Premaratne, Erosha; Power, David A; MacIsaac, Richard J

    2008-01-01

    In late diabetic nephropathy (DN) the initial lowering of albumin excretion rate (AER) with antihypertensive therapy is proportional to the degree of subsequent preservation of glomerular filtration rate (GFR). Whether a similar relationship exists between AER and GFR in early diabetes is not known. The present analysis has compared AER and GFR responses to antihypertensive therapy in 33 published studies (77 treatment groups) of early and late DN in type 1 (T1) and type 2 (T2) diabetes, analyzed on an intention-to-treat basis. Prospective trials were included if the initial change in AER during the first year of therapy and the change in GFR during at least 2 years of follow-up could be estimated from group mean data. The initial % decreases in AER were 5.9 +/- 4.3 (T1), 10.5 +/- 5.4 (T2, normotensive) and 18.4 +/- 6.2 (T2, hypertensive) in early DN and 7.6 +/- 11.1 (T1) and 20.8 +/- 5.5 (T2) in late DN. The corresponding annual % rates of decline of GFR were 2.0 +/- 0.5 (T1), 1.6 +/- 0.5 (T2, normotensive) and 2.1 +/- 0.3 (T2, hypertensive) in early DN and 9.8 +/- 1.5 (T1) and 9.2 +/- 1.1 (T2) in late DN. AER and GFR responses in each treatment group were closely correlated in late nephropathy (T1, r = -0.67, p = 0.03; T2, r = 0.57, p = 0.02) but not in early nephropathy. In contrast to late DN, the initial decrease in AER with antihypertensive therapy was not shown to predict the subsequent rate of decline of GFR in early DN. It follows that assessment of renoprotection during antihypertensive therapy in early nephropathy should be based not only on albuminuria but also on the GFR response. Copyright 2008 S. Karger AG, Basel.

  4. The Role of Early Symptom Trajectories and Pretreatment Variables in Predicting Treatment Response to Cognitive Behavioral Therapy

    Science.gov (United States)

    Lewis, Cara C.; Simons, Anne D.; Kim, Hyoun K.

    2012-01-01

    Objective: Research has focused on 2 different approaches to answering the question, "Which clients will respond to cognitive behavioral therapy (CBT) for depression?" One approach focuses on rates of symptom change within the 1st few weeks of treatment, whereas the 2nd approach looks to pretreatment client variables (e.g., hopelessness) to…

  5. Prediction of acute and late responses to light therapy from vocal (pitch) and self-rated activation in seasonal affective disorder.

    Science.gov (United States)

    Boenink, A D; Bouhuys, A L; Beersma, D G; Meesters, Y

    1997-02-01

    It was hypothesized that pre-treatment activation plays a role in the response to light therapy in Seasonal Affective Disorder (SAD). In 55 SAD patients (DSMIII-R) energetic and tense activation was assessed before light therapy via self-rating (AD-ACL) and voice sound characteristics (mean pitch and variation in pitch). These variables were studied in relation to the "acute" response to 4 days of light therapy (30 min, 10000 lux) and to a "late" response (11 (10) days after light therapy had stopped). Acute response was defined as the percent change in 3 times daily self-rated depressed mood (AMS) with respect to the average of 4 baseline days. "Late" response was defined as the percent change in HRSD or AMS scores between baseline and 11 (10) days after light therapy. It was found that patients having high pitched voices with small variation in this pitch benefitted more from light therapy than the patients with low pitch and large variation in pitch levels. This effect was only significant after the first day of light exposure. No other significant relations were found between baseline activation and acute or late responses to light therapy. Hence, light therapy seems to give extra comfort in "tense" patients, who become rapid responders to light therapy.

  6. Pretreatment Prediction of Individual Rheumatoid Arthritis Patients' Response to Anti-Cytokine Therapy Using Serum Cytokine/Chemokine/Soluble Receptor Biomarkers

    National Research Council Canada - National Science Library

    Uno, Kazuko; Yoshizaki, Kazuyuki; Iwahashi, Mitsuhiro; Yamana, Jiro; Yamana, Seizo; Tanigawa, Miki; Yagi, Katsumi

    2015-01-01

    ...’ speedy recovery and to the clinical use of anti-cytokine therapy. Identifying predictive biomarkers that can assist in matching RA patients with more suitable anti-cytokine treatment was our aim in this report...

  7. [Lead-in period and week 8 as predictive tools for response to boceprevir therapy: a retrospective study of Spanish real clinical practice].

    Science.gov (United States)

    Crespo, Javier; Berenguer, Marina; Pérez, Francisco; Fernández, Inmaculada; González, Olga; Bárcena, Rafael; Buti, María; López, Jesús; Calleja, José Luis

    2015-11-01

    Most discontinuations due to lack of virological response occur during the first few weeks of hepatitis C virus (HCV) triple therapy. Improved knowledge of baseline factors and their correlation with boceprevir decision points may predict treatment success. An observational, retrospective study was conducted to describe the lead-in period as a clinical decision tool in HCV genotype 1 patients treated with boceprevir. Data were collected from the medical records of 186 consecutive patients distributed across 20 Spanish general hospitals. This study included 171 patients. A total of 80% had fibrosis F3/F4, 74% were previously treated, and 26% were treatment-naïve. After the lead-in period, 54.5% of the patients had a reduction of ≥1 log10; this reduction occurred in 52.5% of those with advanced fibrosis. Boceprevir therapy was started in 94% of the patients. Discontinuations at week 4 were limited to null responders with cirrhosis. The baseline factors associated with virological response at week 4 were IL28B, previous response, and fibrosis score. At week 8, HCV-RNA was undetectable in 48.8% of the patients. The correlation between responses at weeks 8 and 12 was 88%. In the Spanish clinical setting, lead-in was mainly used as a clinical decision point for non-responders with cirrhosis. The good correlation between stopping rules at weeks 8 and 12 could be used to anticipate discontinuation, thus saving adverse events and costs. Copyright © 2015 Elsevier España, S.L.U. and AEEH y AEG. All rights reserved.

  8. Predictive and prognostic value of FDG-PET/CT imaging and different response evaluation criteria after primary systemic therapy of breast cancer.

    Science.gov (United States)

    Tőkés, Tímea; Kajáry, Kornélia; Szentmártoni, Gyöngyvér; Lengyel, Zsolt; Györke, Tamás; Torgyík, László; Somlai, Krisztián; Tőkés, Anna-Mária; Kulka, Janina; Dank, Magdolna

    2017-01-01

    (1) To predict pathological complete remission (pCR) and survival after primary systemic therapy (PST) in patients diagnosed with breast cancer by using two different PET/CT based scores: a simplified PERCIST-based PET/CT score (Method 1) and a combined PET/CT score supplemented with the morphological results of the RECIST system (Method 2) and (2) to assess the effect of different breast carcinoma subtypes on tumor response and its evaluation. Eighty-eight patients were enrolled in the study who underwent PET/CT imaging before and after PST. PET/CTs were evaluated by changes in maximum Standardized Uptake Value (SUVmax) and tumor size. Method 1 and 2 were applied to predict pathological complete remission (pCR). Kaplan-Meier analyses for survival were performed. Classification into biological subtypes was performed based on the pre-therapeutic tumor characteristics. A total of 30/88 patients showed pCR (34.1 %). Comparing pCR/non-pCR patient groups, significant differences were detected by changes in SUVmax (p evaluation with Method 2 and not with Method 1. In our study, neither clinical nor pathological CR were predictors of longer progression-free survival. Our results suggest that combined PET/CT criteria are more predictive of pCR. The effect of biological subtypes is significant on pCR rate as well as on the changes in FDG-uptake and morphological tumor response. Response evaluation with combined criteria was also able to reflect the differences between the biological behavior of breast tumor subtypes.

  9. Genotype-Associated Differential NKG2D Expression on CD56+CD3+ Lymphocytes Predicts Response to Pegylated-Interferon/Ribavirin Therapy in Chronic Hepatitis C.

    Science.gov (United States)

    Chu, Po-sung; Ebinuma, Hirotoshi; Nakamoto, Nobuhiro; Sugiyama, Kazuo; Usui, Shingo; Wakayama, Yuko; Taniki, Nobuhito; Yamaguchi, Akihiro; Shiba, Shunsuke; Yamagishi, Yoshiyuki; Wakita, Takaji; Hibi, Toshifumi; Saito, Hidetsugu; Kanai, Takanori

    2015-01-01

    Hepatitis C virus (HCV) genotype 1 infections are significantly more difficult to eradicate with PEG-IFN/ribavirin therapy, compared to HCV genotype 2. The aim of this work is to investigate the difference of immunological impairments underlying this phenomenon. Pre-treatment NKG2D expression on peripheral CD56+CD3+ lymphocytes and CD56+CD3- NK cells from cases of chronic hepatitis C were analyzed and assessed by treatment effect. Two strains of HCV were used to co-incubate with immune cells in vitro. NKG2D expression on peripheral CD56+CD3+ lymphocytes, but not NK cells, was significantly impaired in genotype 1 infection, compared to genotype 2. When peripheral blood mononuclear cells from healthy donors were co-incubated with TNS2J1, a genotype 1b/2a chimera strain, or with JFH1, a genotype 2a strain, genotype-specific decrease of NKG2D on CD56+CD3+ lymphocytes, but not NK cells, was observed. Pre-treatment NKG2D expression on peripheral CD56+CD3+ lymphocytes significantly correlated with reduction in serum HCV RNA levels from week 0 to week 4, and predicted treatment response. Ex vivo stimulation of peripheral CD56+CD3+ lymphocytes showed NKG2D expression-correlated IFN-γ production. In conclusion, Decreased NKG2D expression on CD56+CD3+ lymphocytes in chronic HCV genotype 1 infection predicts inferior treatment response to PEG-IFN/ribavirin therapy compared to genotype 2.

  10. SU-D-207B-07: Development of a CT-Radiomics Based Early Response Prediction Model During Delivery of Chemoradiation Therapy for Pancreatic Cancer

    Energy Technology Data Exchange (ETDEWEB)

    Klawikowski, S; Christian, J; Schott, D; Zhang, M; Li, X [Medical College of Wisconsin, Milwaukee, WI (United States)

    2016-06-15

    =0.9741), and kernel (p=0.8586). Conclusion: We have successfully created a CT-texture based early treatment response prediction model using the CTs acquired during the delivery of chemoradiation therapy for pancreatic cancer. Future testing is required to validate the model with more patient data.

  11. Predicting cognitive behavioral therapy response in social anxiety disorder with anterior cingulate cortex and amygdala during emotion regulation

    Directory of Open Access Journals (Sweden)

    Heide Klumpp

    2017-01-01

    Conclusions: Across forms of regulation, rACC activity predicted responder status whereas amygdala as a neuromarker was limited to implicit regulation. While the direction of effects (enhanced vs. reduced in rACC activity was task-dependent, results suggest SAD patients with deficient regulation benefited more from CBT. Findings support previous studies involving patients with depression and suggest the rACC may be a viable marker of clinical improvement in SAD.

  12. KIR, HLA, and IL28B variant predict response to antiviral therapy in genotype 1 chronic hepatitis C patients in Japan.

    Directory of Open Access Journals (Sweden)

    Yuichi Nozawa

    Full Text Available Natural killer cell responses play a crucial role in virus clearance by the innate immune system. Although the killer immunoglobulin-like receptor (KIR in combination with its cognate human leukocyte antigen (HLA ligand, especially KIR2DL3-HLA-C1, is associated with both treatment-induced and spontaneous clearance of hepatitis C virus (HCV infection in Caucasians, these innate immunity genes have not been fully clarified in Japanese patients. We therefore investigated 16 KIR genotypes along with HLA-B and -C ligands and a genetic variant of interleukin (IL 28B (rs8099917 in 115 chronic hepatitis C genotype 1 patients who underwent pegylated-interferon-α2b (PEG-IFN and ribavirin therapy. HLA-Bw4 was significantly associated with a sustained virological response (SVR to treatment (P = 0.017; odds ratio [OR] = 2.50, , as was the centromeric A/A haplotype of KIR (P = 0.015; OR 3.37. In contrast, SVR rates were significantly decreased in patients with KIR2DL2 or KIR2DS2 (P = 0.015; OR = 0.30, and P = 0.025; OR = 0.32, respectively. Multivariate logistic regression analysis subsequently identified the IL28B TT genotype (P = 0.00009; OR = 6.87, 95% confidence interval [CI] = 2.62 - 18.01, KIR2DL2/HLA-C1 (P = 0.014; OR = 0.24, 95% CI = 0.08 - 0.75, KIR3DL1/HLA-Bw4 (P = 0.008, OR = 3.32, 95% CI = 1.37 - 8.05, and white blood cell count at baseline (P = 0.009; OR = 3.32, 95% CI = 1.35 - 8.16 as independent predictive factors of an SVR. We observed a significant association between the combination of IL28B TT genotype and KIR3DL1-HLA-Bw4 in responders (P = 0.0019, whereas IL28B TT along with KIR2DL2-HLA-C1 was related to a non-response (P = 0.0067. In conclusion, combinations of KIR3DL1/HLA-Bw4, KIR2DL2/HLA-C1, and a genetic variant of the IL28B gene are predictive of the response to PEG-IFN and ribavirin therapy in Japanese patients infected with genotype 1b HCV.

  13. Epstein-Barr virus and Interleukin-28B polymorphism in the prediction of response to interferon therapy in hepatitis C patients.

    Science.gov (United States)

    Zekri, Abdel-Rahman N; Abdullah, Dina; Osman, Ahmed; El-Rouby, Mahmoud N; Zayed, Naglaa; Esmat, Gamal; Elakel, Wafaa; Hafez, Hanan Abdel

    2015-01-01

    In chronic hepatitis C virus (HCV), viral and host factors are known to be predictors for anti-viral therapy. IL-28B genotype strongly influences treatment outcome, while Epstein-Barr virus (EBV) co-infection could accelerate the course of chronic HCV infection. This study was conducted to assess whether EBV co-infection adds to the predictive value of IL-28B. A total of 105 patients with chronic HCV were classified according to their response to treatment into two groups: 38 sustained virological responders (SVRs) and 67 nonresponders (NRs). Collected sera at baseline and follow-up (FUP) were used for assessing EBV antibodies by enzyme-linked immunosorbent assay (ELISA) and the expression of EBV genes (BNLF-1, BZLF-1, and EBER-2) by polymerase chain reaction (PCR). Collected peripheral blood was used for detecting IL-28B rs.12979860 single-nucleotide polymorphism. Regarding IL-28B genotype frequencies, a significant difference (p=0.003) was observed between SVRs (C/C=51.4%, C/T=48.6%, T/T=0%) and NRs (C/C=25%, C/T=55%, T/T=20%). On assessing EBV infection at baseline and FUP, it was found that 61% and 55% were positive, respectively, with no significant difference between SVRs and NRs. As for anti-viral capsid antigen (VCA) antibodies, the NRs had significantly higher baseline anti-VCA immunoglobulin M (IgM) levels than SVRs (p=0.01). While FUP anti-Epstein-Barr nuclear antigen-1 (EBNA-1) IgG reported a significant decline within SVR patients (p=0.02), neither baseline nor FUP anti-VCA IgG levels showed a statistically significant viral response. Finally, on comparing EBV markers with CC versus CT and TT genotypes, it was found that FUP anti-VCA IgG levels were significantly increased in CC genotype (p=0.003). Interleukin-28B polymorphism could be a possible predictor of response to pegylated interferon/ribavirin therapy (PEG-IFN/RBV). Furthermore, co-infection with EBV did not affect the response to IFN-based therapy in HCV-infected patients. Copyright © 2015

  14. Baseline resistance to nucleoside reverse transcriptase inhibitors fails to predict virologic response to combination therapy in children (PACTG 338

    Directory of Open Access Journals (Sweden)

    McIntosh Kenneth

    2007-02-01

    Full Text Available Abstract Background The association between baseline drug resistance mutations and subsequent increase in viral failure has not been established for HIV-infected children. We evaluated drug resistance mutations at 39 codon sites (21 protease inhibitor (PI resistant codons and 18 nucleoside reverse transcriptase inhibitor (NRTI resistant codons for 92 clinically stable NRTI-experienced, PI-naive HIV-infected children 2 to 17 years of age who were initiating new therapy with ritonavir plus zidovudine (ZDV and lamivudine or plus stavudine. The association between baseline drug resistance mutations and subsequent viral failure after 12 and 24 weeks of highly active antiretroviral therapy (HAART was studied. Results There were few primary PI associated mutations in this PI-naïve population, but 84% had NRTI mutations – codons 215 (66%, 41 (42%, 67 (37%, 210 (33% and 70 (32%. None of the specific baseline drug resistance mutations were associated with a higher rate of virologic failure after 12 or 24 weeks of HAART. Median week 12 viral load decreased as the total number of NRTI mutations at baseline increased (P = 0.006. Specifically, a higher level of baseline ZDV resistance mutation was associated with a decrease in viral failure after 12 weeks on a ZDV-containing HAART regimen (P = 0.017. Conclusion No increase was seen in the rate of viral failure after HAART associated with the presence of resistance mutations at baseline. This paradoxical result may be due to adherence, replicative capacity, or ZDV hypersusceptibility to the new regimen.

  15. Limitations of serum ferritin to predict liver iron concentration responses to deferasirox therapy in patients with transfusion-dependent thalassaemia.

    Science.gov (United States)

    Porter, John B; Elalfy, Mohsen; Taher, Ali; Aydinok, Yesim; Lee, Szu-Hee; Sutcharitchan, Pranee; El-Ali, Ali; Han, Jackie; El-Beshlawy, Amal

    2017-03-01

    In transfusion-dependent anaemias, while absolute serum ferritin levels broadly correlate with liver iron concentration (LIC), relationships between trends in these variables are unclear. These relationships are important because serum ferritin changes are often used to adjust or switch chelation regimens when liver magnetic resonance imaging (MRI) is unavailable. This post hoc analysis of the EPIC study compared serum ferritin and LIC in 317 patients with transfusion-dependent thalassaemia before and after 1 yr of deferasirox. Serum ferritin responses (decreases) occurred in 73% of patients, 80% of whom also have decreased LIC. However, 52% of patients without a serum ferritin response did decrease LIC and by >1 mg Fe/g dw (median 3.9) in 77% of cases. Absolute serum ferritin and LIC values correlated significantly only when serum ferritin was <4000 ng/mL (r = 0.59; P < 0.0001) and not at higher levels (≥4000 ng/mL; r = 0.19). Serum ferritin response was accompanied by decreased LIC in 89% and 70% of cases when serum ferritin was <4000 or ≥4000 ng/mL, respectively. As serum ferritin non-response was associated with LIC decrease in over half of patients, use of liver MRI may be particularly useful for differentiating true from apparent non-responders to deferasirox based on serum ferritin trends alone. © 2016 The Authors. European Journal of Haematology Published by John Wiley & Sons Ltd.

  16. Are Fusion Transcripts in Relapsed/Metastatic Head and Neck Cancer Patients Predictive of Response to Anti-EGFR Therapies?

    Directory of Open Access Journals (Sweden)

    Paolo Bossi

    2017-01-01

    Full Text Available Prediction of benefit from combined chemotherapy and the antiepidermal growth factor receptor cetuximab is a not yet solved question in head and neck squamous cell carcinoma (HNSCC. In a selected series of 14 long progression-free survival (PFS and 26 short PFS patients by whole gene and microRNA expression analysis, we developed a model potentially predictive of cetuximab sensitivity. To better decipher the “omics” profile of our patients, we detected transcript fusions by RNA-seq through a Pan-Cancer panel targeting 1385 cancer genes. Twenty-seven different fusion transcripts, involving mRNA and long noncoding RNA (lncRNA, were identified. The majority of fusions (81% were intrachromosomal, and 24 patients (60% harbor at least one of them. The presence/absence of fusions and the presence of more than one fusion were not related to outcome, while the lncRNA-containing fusions resulted enriched in long PFS patients (P=0.0027. The CD274-PDCD1LG2 fusion was present in 7/14 short PFS patients harboring fusions and was absent in long PFS patients (P=0.0188. Among the short PFS patients, those harboring this fusion had the worst outcome (P=0.0172 and increased K-RAS activation (P=0.00147. The associations between HNSCC patient’s outcome following cetuximab treatment and lncRNA-containing fusions or the CD274-PDCD1LG2 fusion deserve validation in prospective clinical trials.

  17. Prediction of acute and late responses to light therapy from vocal (pitch) and self-rated activation in seasonal affective disorder

    NARCIS (Netherlands)

    Boenink, AD; Bouhuys, AL; Beersma, DGM; Meesters, Y

    It was hypothesized that pre-treatment activation plays a role in the response to light therapy in Seasonal Affective Disorder (SAD). In 55 SAD patients (DSMIII-R) energetic and tense activation was assessed before light therapy via self-rating (AD-ACL) and voice sound characteristics (mean pitch

  18. Ursodeoxycholic acid therapy in intrahepatic cholestasis of pregnancy: Results in real-world conditions and factors predictive of response to treatment.

    Science.gov (United States)

    Bacq, Yannick; le Besco, Matthieu; Lecuyer, Anne-Isabelle; Gendrot, Chantal; Potin, Jérôme; Andres, Christian R; Aubourg, Alexandre

    2017-01-01

    Ursodeoxycholic acid (UDCA) therapy is commonly used in intrahepatic cholestasis of pregnancy (ICP). To evaluate the efficacy and tolerance of UDCA in real-world conditions and to search for factors predictive of response to treatment. This observational study included 98 consecutive patients suffering from pruritus during pregnancy associated with increased ALT levels or total bile acid (TBA) concentrations, without other causes of cholestasis. The entire ABCB4 gene coding sequence was analyzed by DNA sequencing. UDCA was prescribed until delivery in all patients (mean dose 14.0mg/kg/day; mean duration 30.4 days). Pruritus improved in 75/98 (76.5%) patients, and totally disappeared before delivery in 25/98 (25.5%). After 2-3 weeks of treatment, ALT levels decreased by more than 50% of base line in 67/86 (77.9%) patients and normalized in 34/86 (39.5%), and TBA concentrations decreased in 28/81 (34.6%). Only one patient stopped the treatment before delivery. On multivariate analysis, ALT >175IU/l before treatment was associated with improvement of pruritus (OR 2.97, 95% CI 1.12-7.89, P=0.029) and with decreased ALT (OR 18.61, 95% CI 3.94-87.99, P=0.0002). ABCB4 gene mutation was not associated with response to treatment. This study supports the use of UDCA as first line therapy in ICP. Copyright © 2016 Editrice Gastroenterologica Italiana S.r.l. Published by Elsevier Ltd. All rights reserved.

  19. Ku70, Ku80, and sClusterin: A Cluster of Predicting Factors for Response to Neoadjuvant Chemoradiation Therapy in Patients With Locally Advanced Rectal Cancer

    Energy Technology Data Exchange (ETDEWEB)

    Pucci, Sabina, E-mail: sabina.pucci@uniroma2.it; Polidoro, Chiara; Joubert, Alessandro; Mastrangeli, Francesca; Tolu, Barbara; Benassi, Michaela; Fiaschetti, Valeria; Greco, Laura; Miceli, Roberto; Floris, Roberto; Novelli, Giuseppe; Orlandi, Augusto; Santoni, Riccardo

    2017-02-01

    Purpose: The identification of predictive biomarkers for neoadjuvant chemoradiation therapy (CRT) is a current clinical need. The heterodimer Ku70/80 plays a critical role in DNA repair and cell death induction after damage. The aberrant expression and localization of these proteins fail to control DNA repair and apoptosis. sClusterin is the Ku70 partner that sterically inhibits Bax-dependent cell death after damage in some pathologic conditions. This study sought to evaluate the molecular relevance of Ku70-Ku80-Clu as a molecular cluster predicting the response to neoadjuvant CRT in patients with locally advanced rectal cancer (LARC). Methods and Materials: Patients enrolled in this study underwent preoperative CRT followed by surgical excision. A retrospective study based on individual response, evaluated by computed tomography and diffusion-weighted magnetic resonance imaging, identified responder (56%) and no-responder patients (44%). Ku70/80 and Clu expression were observed in biopsy specimens obtained before and after treatment with neoadjuvant CRT from the same LARC patients. In vitro studies before and after irradiation were also performed on radioresistant (SW480) and radiosensitive (SW620) colorectal cancer cell lines, mimicking sensitive or resistant tumor behavior. Results: We found a conventional nuclear localization of Ku70/80 in pretherapeutic tumor biopsies of responder patients, in agreement with their role in DNA repair and regulating apoptosis. By contrast, in the no-responder population we observed an unconventional overexpression of Ku70 in the cytoplasm (P<.001). In this context we also overexpression of sClu in the cytoplasm, which accorded with its role in stabilizing of Bax-Ku70 complex, inhibiting Bax-dependent apoptosis. Strikingly, Ku80 in these tumor tissues was lost (P<.005). In vitro testing of colon cancer cells finally confirmed the results observed in tumor biopsy specimens, proving that Ku70/80-Clu deregulation is extensively

  20. SU-F-303-05: DCE-MRI Before and During Treatment for Prediction of Concurrent Chemotherapy and Radiation Therapy Response in Head and Neck Cancer

    Energy Technology Data Exchange (ETDEWEB)

    Liu, Y; Diwanji, T; Zhang, B; Zhuo, J; Gullapalli, R; Morales, R; D’Souza, W [University of Maryland School of Medicine, Baltimore, MD (United States)

    2015-06-15

    Purpose: To determine the ability of pharmacokinetic parameters derived from dynamic contrast-enhanced MRI (DCE- MRI) acquired before and during concurrent chemotherapy and radiation therapy to predict clinical response in patients with head and neck cancer. Methods: Eleven patients underwent a DCE-MRI scan at three time points: 1–2 weeks before treatment, 4–5 weeks after treatment initiation, and 3–4 months after treatment completion. Post-processing of MRI data included correction to reduce motion artifacts. The arterial input function was obtained by measuring the dynamic tracer concentration in the jugular veins. The volume transfer constant (Ktrans), extracellular extravascular volume fraction (ve), rate constant (Kep; Kep = Ktrans/ve), and plasma volume fraction (vp) were computed for primary tumors and cervical nodal masses. Patients were categorized into two groups based on response to therapy at 3–4 months: responders (no evidence of disease) and partial responders (regression of disease). Responses of the primary tumor and nodes were evaluated separately. A linear classifier and receiver operating characteristic curve analyses were used to determine the best model for discrimination of responders from partial responders. Results: When the above pharmacokinetic parameters of the primary tumor measured before and during treatment were incorporated into the linear classifier, a discriminative accuracy of 88.9%, with sensitivity =100% and specificity = 66.7%, was observed between responders (n=6) and partial responders (n=3) for the primary tumor with the corresponding accuracy = 44.4%, sensitivity = 66.7%, and specificity of 0% for nodal masses. When only pre-treatment parameters were used, the accuracy decreased to 66.7%, with sensitivity = 66.7% and specificity = 66.7% for the primary tumor and decreased to 33.3%, sensitivity of 50%, and specificity of 0% for nodal masses. Conclusion: Higher accuracy, sensitivity, and specificity were obtained

  1. Monitoring Tumor Response to Carbogen Breathing by Oxygen-Sensitive Magnetic Resonance Parameters to Predict the Outcome of Radiation Therapy: A Preclinical Study

    Energy Technology Data Exchange (ETDEWEB)

    Cao-Pham, Thanh-Trang; Tran, Ly-Binh-An; Colliez, Florence; Joudiou, Nicolas [Université Catholique de Louvain, Louvain Drug Research Institute, Biomedical Magnetic Resonance Research Group, Brussels (Belgium); El Bachiri, Sabrina [Université Catholique de Louvain, IMMAQ Technological Platform, Methodology and Statistical Support, Louvain-la-Neuve (Belgium); Grégoire, Vincent [Université Catholique de Louvain, Institute of Experimental and Clinical Research, Center for Molecular Imaging, Radiotherapy and Oncology, Brussels (Belgium); Levêque, Philippe; Gallez, Bernard [Université Catholique de Louvain, Louvain Drug Research Institute, Biomedical Magnetic Resonance Research Group, Brussels (Belgium); Jordan, Bénédicte F., E-mail: benedicte.jordan@uclouvain.be [Université Catholique de Louvain, Louvain Drug Research Institute, Biomedical Magnetic Resonance Research Group, Brussels (Belgium)

    2016-09-01

    Purpose: In an effort to develop noninvasive in vivo methods for mapping tumor oxygenation, magnetic resonance (MR)-derived parameters are being considered, including global R{sub 1}, water R{sub 1}, lipids R{sub 1}, and R{sub 2}*. R{sub 1} is sensitive to dissolved molecular oxygen, whereas R{sub 2}* is sensitive to blood oxygenation, detecting changes in dHb. This work compares global R{sub 1}, water R{sub 1}, lipids R{sub 1}, and R{sub 2}* with pO{sub 2} assessed by electron paramagnetic resonance (EPR) oximetry, as potential markers of the outcome of radiation therapy (RT). Methods and Materials: R{sub 1}, R{sub 2}*, and EPR were performed on rhabdomyosarcoma and 9L-glioma tumor models, under air and carbogen breathing conditions (95% O{sub 2}, 5% CO{sub 2}). Because the models demonstrated different radiosensitivity properties toward carbogen, a growth delay (GD) assay was performed on the rhabdomyosarcoma model and a tumor control dose 50% (TCD50) was performed on the 9L-glioma model. Results: Magnetic resonance imaging oxygen-sensitive parameters detected the positive changes in oxygenation induced by carbogen within tumors. No consistent correlation was seen throughout the study between MR parameters and pO{sub 2}. Global and lipids R{sub 1} were found to be correlated to pO{sub 2} in the rhabdomyosarcoma model, whereas R{sub 2}* was found to be inversely correlated to pO{sub 2} in the 9L-glioma model (P=.05 and .03). Carbogen increased the TCD50 of 9L-glioma but did not increase the GD of rhabdomyosarcoma. Only R{sub 2}* was predictive (P<.05) for the curability of 9L-glioma at 40 Gy, a dose that showed a difference in response to RT between carbogen and air-breathing groups. {sup 18}F-FAZA positron emission tomography imaging has been shown to be a predictive marker under the same conditions. Conclusion: This work illustrates the sensitivity of oxygen-sensitive R{sub 1} and R{sub 2}* parameters to changes in tumor oxygenation. However, R{sub 1

  2. 18F-Alfatide II and 18F-FDG Dual Tracer Dynamic PET for Parametric, Early Prediction of Tumor Response to Therapy

    Science.gov (United States)

    Guo, Jinxia; Guo, Ning; Lang, Lixin; Kiesewetter, Dale O.; Xie, Qingguo; Li, Quanzheng; Eden, Henry S.; Niu, Gang; Chen, Xiaoyuan

    2014-01-01

    analysis in tumors showed significant decreases. For Abraxane therapy of MDA-MB-435 tumors, significant decrease was only observed with 18F-Alfatide II Bp value from kinetic analysis but not 18F-FDG influx. Conclusion The parameters fitted with compartmental modeling from the dual tracer dynamic imaging are consistent with those from single tracer imaging, substantiating the feasibility of this methodology. Even though no significant differences in tumor size were found until 5 days after doxorubicin treatment started, at day 3 there were already substantial differences in 18F-Alfatide II Bp and 18F-FDG influx rate. Dual tracer imaging can measure 18F-Alfatide II Bp value and 18F-FDG influx simultaneously to evaluate tumor angiogenesis and metabolism. Such changes are known to precede anatomical changes, and thus parametric imaging may offer the promise of early prediction of therapy response. PMID:24232871

  3. (18)F-alfatide II and (18)F-FDG dual-tracer dynamic PET for parametric, early prediction of tumor response to therapy.

    Science.gov (United States)

    Guo, Jinxia; Guo, Ning; Lang, Lixin; Kiesewetter, Dale O; Xie, Qingguo; Li, Quanzheng; Eden, Henry S; Niu, Gang; Chen, Xiaoyuan

    2014-01-01

    or (18)F-FDG were observed, both (18)F-alfatide II Bp and (18)F-FDG influx from kinetic analysis in tumors showed significant decreases. For therapy of MDA-MB-435 tumors with paclitaxel protein-bound particles, a significant decrease was observed only with (18)F-alfatide II Bp value from kinetic analysis but not (18)F-FDG influx. The parameters fitted with compartmental modeling from the dual-tracer dynamic imaging are consistent with those from single-tracer imaging, substantiating the feasibility of this methodology. Even though no significant differences in tumor size were found until 5 d after doxorubicin treatment started, at day 3 there were already substantial differences in (18)F-alfatide II Bp and (18)F-FDG influx rate. Dual-tracer imaging can measure (18)F-alfatide II Bp value and (18)F-FDG influx simultaneously to evaluate tumor angiogenesis and metabolism. Such changes are known to precede anatomic changes, and thus parametric imaging may offer the promise of early prediction of therapy response.

  4. Development and Internal Validation of a Clinical Risk Score to Predict Pain Response After Palliative Radiation Therapy in Patients With Bone Metastases

    NARCIS (Netherlands)

    van der Velden, JM; Peters, Max; Verlaan, Jorrit Jan|info:eu-repo/dai/nl/269057285; Versteeg, Anne L.; Zhang, Liying; Tsao, May; Danjoux, Cyril; Barnes, Elizabeth; van Vulpen, Marco|info:eu-repo/dai/nl/250581035; Chow, Edward; Verkooijen, Helena M.|info:eu-repo/dai/nl/213707705

    2017-01-01

    Purpose To investigate the relationship between patient and tumor characteristics and pain response in patients with metastatic bone disease, and construct and internally validate a clinical prediction model for pain response to guide individualized treatment decision making. Material and Methods A

  5. A Personalized Approach to Biological Therapy Using Prediction of Clinical Response Based on MRP8/14 Serum Complex Levels in Rheumatoid Arthritis Patients.

    Directory of Open Access Journals (Sweden)

    S C Nair

    Full Text Available Measurement of MRP8/14 serum levels has shown potential in predicting clinical response to different biological agents in rheumatoid arthritis (RA. We aimed to develop a treatment algorithm based on a prediction score using MRP8/14 measurements and clinical parameters predictive for response to different biological agents.Baseline serum levels of MRP8/14 were measured in 170 patients starting treatment with infliximab, adalimumab or rituximab. We used logistic regression analysis to develop a predictive score for clinical response at 16 weeks. MRP8/14 levels along with clinical variables at baseline were investigated. We also investigated how the predictive effect of MRP8/14 was modified by drug type. A treatment algorithm was developed based on categorizing the expected response per drug type as high, intermediate or low for each patient and optimal treatment was defined. Finally, we present the utility of using this treatment algorithm in clinical practice.The probability of response increased with higher baseline MRP8/14 complex levels (OR = 1.39, differentially between the TNF-blockers and rituximab (OR of interaction term = 0.78, and also increased with higher DAS28 at baseline (OR = 1.28. Rheumatoid factor positivity, functional disability (a higher HAQ, and previous use of a TNF-inhibitor decreased the probability of response. Based on the treatment algorithm 80 patients would have been recommended for anti-TNF treatment, 8 for rituximab, 13 for another biological treatment (other than TNFi or rituximab and for 69 no recommendation was made. The predicted response rates matched the observed response in the cohort well. On group level the predicted response based on the algorithm resulted in a modest 10% higher response rate in our cohort with much higher differences in response probability in individual patients treated contrary to treatment recommendation.Prediction of response using MRP8/14 levels along with clinical predictors has

  6. Prediction of Response to Immune Checkpoint Inhibitor Therapy Using Early-Time-Point 18F-FDG PET/CT Imaging in Patients with Advanced Melanoma.

    Science.gov (United States)

    Cho, Steve Y; Lipson, Evan J; Im, Hyung-Jun; Rowe, Steven P; Gonzalez, Esther Mena; Blackford, Amanda; Chirindel, Alin; Pardoll, Drew M; Topalian, Suzanne L; Wahl, Richard L

    2017-09-01

    The purpose of this study was to evaluate 18F-FDG PET/CT scanning as an early predictor of response to immune checkpoint inhibitors (ICIs) in patients with advanced melanoma. Methods: Twenty patients with advanced melanoma receiving ICI prospectively underwent 18F-FDG PET/CT at 3 scan intervals: before treatment initiation (SCAN-1), at days 21-28 (SCAN-2), and at 4 mo (SCAN-3). This study was approved by the institutional review board, and informed consent was received from all patients who were enrolled between April 2012 and December 2013. Tumor response at each posttreatment time point was assessed according to RECIST 1.1, immune-related response criteria, PERCIST (PERCIST 1.0), and European Organization for Research and Treatment of Cancer (EORTC) criteria. Performance characteristics of each metric to predict best overall response (BOR) at ≥ 4 mo were assessed. Results: Twenty evaluable patients were treated with ipilimumab (n = 16), BMS-936559 (n = 3), or nivolumab (n = 1). BOR at ≥ 4 mo included complete response (n = 2), partial response (n = 2), stable disease (n = 1), and progressive disease (n = 15). Response evaluations at SCAN-2 using RECIST 1.1, immune-related response criteria, PERCIST, and EORTC criteria demonstrated accuracies of 75%, 70%, 70%, and 65%, respectively, to predict BOR at ≥ 4 mo. Interestingly, the optimal PERCIST and EORTC threshold values at SCAN-2 to predict BOR were >15.5% and >14.7%, respectively. By combining anatomic and functional imaging data collected at SCAN-2, we developed criteria to predict eventual response to ICI with 100% sensitivity, 93% specificity, and 95% accuracy. Conclusion: Combining functional and anatomic imaging parameters from 18F-FDG PET/CT scans performed early in ICI appears predictive for eventual response in patients with advanced melanoma. These findings require validation in larger cohorts. © 2017 by the Society of Nuclear Medicine and Molecular Imaging.

  7. The myocardial ischemia evaluated by real-time contrast echocardiography may predict the response to cardiac resynchronization therapy: a large animal study.

    Directory of Open Access Journals (Sweden)

    Yongle Chen

    Full Text Available Evidence-based criteria for applying cardiac resynchronization therapy (CRT in patients with ischemic cardiomyopathy are still scarce. The aim of the present study was to evaluate the predictive value of real-time myocardial contrast echocardiography (RT-MCE in a preclinical canine model of ischemic cardiomyopathy who received CRT. Ischemic cardiomyopathy was produced by ligating the first diagonal branch in 20 beagles. Dogs were subsequently divided into two groups that were either treated with bi-ventricular pacing (CRT group or left untreated (control group. RT-MCE was performed at baseline, before CRT, and 4 weeks after CRT. Two-dimensional speckle tracking imaging was used to evaluate the standard deviation of circumferential (Cir12SD, radial (R12SD, and longitudinal (L12SD strains of left ventricular segments at basal as well as middle levels. Four weeks later, the Cir12SD, R12SD, and myocardial blood flow (MBF of the treated group were significantly improved compared to their non-CRT counterparts. Furthermore, MBF values measured before CRT were significantly higher in responders than in non-responders to bi-ventricular pacing. Meanwhile, no significant differences were observed between the responder and non-responder groups in terms of Cir12SD, R12SD, and L12SD. A high degree of correlation was found between MBF values before CRT and LVEF after CRT. When MBF value>24.9 dB/s was defined as a cut-off point before CRT, the sensitivity and specificity of RT-MCE in predicting the response to CRT were 83.3% and 100%, respectively. Besides, MBF values increased significantly in the CRT group compared with the control group after 4 weeks of pacing (49.8±15.5 dB/s vs. 28.5±4.6 dB/s, p<0.05. Therefore, we considered that myocardial perfusion may be superior to standard metrics of LV synchrony in selecting appropriate candidates for CRT. In addition, CRT can improve myocardial perfusion in addition to cardiac synchrony, especially in the setting

  8. Presence of left ventricular contractile reserve predicts midterm response to cardiac resynchronization therapy--results from the LOw dose DObutamine stress-echo test in Cardiac Resynchronization Therapy (LODO-CRT) trial.

    Science.gov (United States)

    Muto, Carmine; Gasparini, Maurizio; Neja, Carlo Peraldo; Iacopino, Saverio; Davinelli, Mario; Zanon, Francesco; Dicandia, Cosimo; Distefano, Giuseppe; Donati, Roberto; Calvi, Valeria; Denaro, Alessandra; Tuccillo, Bernardino

    2010-11-01

    Cardiac resynchronization therapy (CRT) is effective in selected patients with heart failure (HF). Nevertheless, the nonresponder rate remains high. The low-dose dobutamine stress-echo (DSE) test detects the presence of left ventricular (LV) contractile reserve (LVCR) in HF patients of any etiology and may be useful in predicting response to resynchronization. The purpose of this study was to present the results of the LODO-CRT trial, which evaluated whether LVCR presence at baseline increases the chances of response to CRT. LODO-CRT is a multicenter prospective study that enrolled CRT candidates according to guidelines. LVCR presence was defined as an LV ejection fraction increase >5 units during DSE test. CRT response is assessed at 6-month follow-up as an LV end-systolic volume reduction ≥10%. Two hundred seventy-one patients were enrolled. The DSE test was feasible without complications in 99% of patients. Nine patients died from noncardiac disease, and 31 presented inadequate data. Two hundred thirty-one patients were included in the analysis. Mean patient age was 67 ± 10 years; 95% were in New York Heart Association class III, and 42% had HF of ischemic etiology. Mean QRS and LV ejection fraction were 147 ± 25 ms and 27% ± 6%, respectively. LVCR presence was found in 185 subjects (80%). At follow-up, 170 (74%) patients responded to CRT, 145/185 in the group with LVCR (78%) and 25/46 (54%) in the group without LVCR. Difference in responder proportion to CRT was 24% (P <.001). Reported test sensitivity is 85%. The DSE test in CRT candidates is safe and feasible. LVCR presence at baseline increases the chances of response to CRT. Copyright © 2010 Heart Rhythm Society. Published by Elsevier Inc. All rights reserved.

  9. Assessment of response to anti-angiogenic targeted therapy in pulmonary metastatic renal cell carcinoma: R2* value as a predictive biomarker

    Energy Technology Data Exchange (ETDEWEB)

    Wu, Guangyu; Liu, Guiqin; Suo, Shiteng; Liu, Xiaosheng; Xu, Jianrong [Shanghai Jiao Tong University, Department of Radiology, Renji Hospital, School of Medicine, Shanghai (China); Kong, Wen; Zhang, Jin [Shanghai Jiao Tong University, Department of Urinary Surgery, Renji Hospital, School of Medicine, Shanghai (China); Qu, Jianxun [GE Healthcare, Shanghai (China)

    2017-09-15

    To evaluate the utility of MR R2*-mapping and the optimal time-point for assessing the response of pulmonary metastatic renal cell carcinoma (mRCC) to anti-angiogenic targeted therapy (aATT). The exploration-sample group and the validation-sample group consisted of 22 and 16 patients. The parameters of MR R2*-mapping, including the R2* value at each time-point (R2*{sub base}, R2*{sub 1cyc} and R2*{sub 2cyc}) and change between different time-points (R2*{sub (1cyc-base)/base}, R2*{sub (2cyc-base)/base} and R2*{sub (2cyc-1cyc)/1cyc}), were evaluated with a receiver-operating-characteristic analysis, and a cut-off value derived from the clinical outcome was applied to the Kaplan-Meier method to assess the value of R2* mapping and Response-Evaluation-Criteria in Solid Tumours (RECIST) during treatment evaluation. The inter-, intra-observer agreements and inter-scan consistency were excellent (p > 0.80). For the exploration-sample group, the areas under the curve for the parameters of MR R2* mapping were 0.55, 0.60, 0.83, 0.64, 0.88 and 0.83 for R2*{sub base}, R2*{sub 1cyc}, R2*{sub 2cyc}, R2*{sub (1cyc-base)/base}, R2*{sub (2cyc-base)/base} and R2*{sub (2cyc-1cyc)/1cyc.} For the validation-sample, R2*{sub (2cyc-base)/base} better predicted progression-free survival (p = 0.03) than RECIST and other R2* mapping parameters with a lower p value. Assessing aATT outcome based on changes in the R2* value between baseline and second treatment is more accurate than assessment at other time-points and assessment based on the RECIST. (orig.)

  10. Modeling cancer-immune responses to therapy.

    Science.gov (United States)

    dePillis, L G; Eladdadi, A; Radunskaya, A E

    2014-10-01

    Cancer therapies that harness the actions of the immune response, such as targeted monoclonal antibody treatments and therapeutic vaccines, are relatively new and promising in the landscape of cancer treatment options. Mathematical modeling and simulation of immune-modifying therapies can help to offset the costs of drug discovery and development, and encourage progress toward new immunotherapies. Despite advances in cancer immunology research, questions such as how the immune system interacts with a growing tumor, and which components of the immune system play significant roles in responding to immunotherapy are still not well understood. Mathematical modeling and simulation are powerful tools that provide an analytical framework in which to address such questions. A quantitative understanding of the kinetics of the immune response to treatment is crucial in designing treatment strategies, such as dosing, timing, and predicting the response to a specific treatment. These models can be used both descriptively and predictively. In this chapter, various mathematical models that address different cancer treatments, including cytotoxic chemotherapy, immunotherapy, and combinations of both treatments, are presented. The aim of this chapter is to highlight the importance of mathematical modeling and simulation in the design of immunotherapy protocols for cancer treatment. The results demonstrate the power of these approaches in explaining determinants that are fundamental to cancer-immune dynamics, therapeutic success, and the development of efficient therapies.

  11. A computer-aided diagnosis (CAD) scheme for pretreatment prediction of pathological response to neoadjuvant therapy using dynamic contrast-enhanced MRI texture features.

    Science.gov (United States)

    Giannini, Valentina; Mazzetti, Simone; Marmo, Agnese; Montemurro, Filippo; Regge, Daniele; Martincich, Laura

    2017-08-01

    To assess whether a computer-aided, diagnosis (CAD) system can predict pathological Complete Response (pCR) to neoadjuvant chemotherapy (NAC) prior to treatment using texture features. Response to treatment of 44 patients was defined according to the histopatology of resected tumour and extracted axillary nodes in two ways: (a) pCR+ (Smith's Grade = 5) vs pCR- (Smith's Grade < 5); (b) pCRN+ (pCR+ and absence of residual lymph node metastases) vs pCRN - . A CAD system was developed to: (i) segment the breasts; (ii) register the DCE-MRI sequence; (iii) detect the lesion and (iv) extract 27 3D texture features. The role of individual texture features, multiparametric models and Bayesian classifiers in predicting patients' response to NAC were evaluated. A cross-validated Bayesian classifier fed with 6 features was able to predict pCR with a specificity of 72% and a sensitivity of 67%. Conversely, 2 features were used by the Bayesian classifier to predict pCRN, obtaining a sensitivity of 69% and a specificity of 61%. A CAD scheme, that extracts texture features from an automatically segmented 3D mask of the tumour, could predict pathological response to NAC. Additional research should be performed to validate these promising results on a larger cohort of patients and using different classification strategies. Advances in knowledge: This is the first study assessing the role of an automatic CAD system in predicting the pathological response to NAC before treatment. Fully automatic methods represent the backbone of standardized analysis and may help in timely managing patients candidate to NAC.

  12. Serum metabolites predict response to angiotensin II receptor blockers in patients with diabetes mellitus

    DEFF Research Database (Denmark)

    Pena, Michelle J; Heinzel, Andreas; Rossing, Peter

    2016-01-01

    BACKGROUND: Individual patients show a large variability in albuminuria response to angiotensin receptor blockers (ARB). Identifying novel biomarkers that predict ARB response may help tailor therapy. We aimed to discover and validate a serum metabolite classifier that predicts albuminuria response...

  13. Do emotion regulation, attentional control, and attachment style predict response to cognitive behavioral therapy for anxiety disorders? – an investigation in clinical settings

    DEFF Research Database (Denmark)

    Nielsen, Sara Kerstine Kaya; Hageman, Ida; Petersen, Anders

    2018-01-01

    Objective: Approximately, 50% of all individuals with anxiety disorders do not benefit from the “gold standard” treatment, namely cognitive behavioral therapy (CBT). Reliable predictors of treatment effect are lacking. The primary aim of this study was to investigate the predictive value of emotion...... regulation, attentional control, and attachment style for group-based CBT outcomes in routine clinical settings. Method: A total of 76 patients with anxiety disorders received manual-based group CBT at psychiatric outpatient clinics. Emotion regulation, attachment style, and attentional control were assessed...... with self-report measures and with an experimental computer-based attentional control task at baseline. The severity of anxiety was assessed at intake, post-treatment, and at a 6-month follow-up. Results: Attentional control, emotion regulation, and attachment avoidance did not predict treatment outcomes...

  14. Cognition and quality of life in clinically isolated syndrome patients starting a disease modifying therapy in the QUALICIS study may not predict treatment response at one year.

    Science.gov (United States)

    Cohen, Mikael; Brochet, Bruno; Clavelou, Pierre; Le Page, Emmanuelle; Vermersch, Patrick; Tourbah, Ayman; Moreau, Thibault; Joly, Héloïse; Sakarovitch, Charlotte; Lebrun, Christine

    2017-11-15

    Cognition and health-related quality of life (HRQoL) are early involved in multiple sclerosis (MS). The aim of QUALICIS study was to monitor cognition and HRQoL prospectively in a cohort of clinically isolated syndrome (CIS) patients starting a treatment with subcutaneous beta-1b interferon as a first disease modifying treatment (DMT), and to assess their correlation with the clinical outcome 6years later. Relapse history, EDSS and yearly standardized brain MRI data were also collected. 37 patients were included. Cognition and HRQoL remained stable over treatment period. At baseline, we found that SDMT was moderately correlated to T2 lesion load (r=-0.47, p=0.04). Baseline SDMT was predictive of HRQoL at year 2 (r=0.53, p=0.02). Regarding 6-year outcome, the most specific predictive factor of favorable outcome was achieving "No Evidence of Disease Activity" (NEDA) status at year 1. In this group, all the patients had a stable EDSS score and none switched to a second line therapy. In the "non-NEDA" group, 44% of patients experienced EDSS worsening and 38.9% switched to a second line therapy. The number of gadolinium enhancing lesions on baseline scan was the only predictive factor of poor outcome in this subgroup of patients (2 vs. 0.13, p=0.03). Our results suggest that NEDA at 1year could be used to predict long term outcome after initiation of DMT in CIS. For non-NEDA patients, monitoring SDMT and brain atrophy could be potentially relevant, but this should be confirmed on a larger sample. Copyright © 2017 Elsevier B.V. All rights reserved.

  15. Baseline Hepatitis B Virus DNA Level is a Promising Factor for Predicting the 3 (rd) Month Virological Response to Entecavir Therapy: A Study of Strict Defined Hepatitis B virus Induced Cirrhosis.

    Science.gov (United States)

    Xu, Yang; Wu, Xiao-Ning; Shi, Yi-Wen; Wei, Wei; Yang, Ai-Ting; Sun, Ya-Meng; Zhao, Wen-Shan; You, Hong

    2015-07-20

    Cirrhosis is a common complication of chronic hepatitis B. It remains unclear if viral and biochemical parameters at baseline affect virological response to entecavir and therefore warrant investigation. In the present study, we aimed to evaluate the efficacy of entecavir therapy by monitoring virological response at the end of the 3 rd month of treatment and try to figure out whether baseline factors could help predict it in a cohort of hepatitis B virus (HBV) compensated cirrhosis patients and to determine the cut-off value of a predicting parameter. A total of 91 nucleos(t)ide-naïve patients with HBV induced cirrhosis (compensatory stage) were enrolled in a prospective cohort. HBV DNA and alanine aminotransferase (ALT) were tested at baseline and monitored every 3-6 months after starting therapy. Of all 91 patients, the median follow-up time was 12 (9-24) months. Overall, 64 patients (70.3%) achieved virological response in the 3 rd month. Univariate analysis showed that the 3 rd month virological response can be predicted by baseline HBV DNA levels (P rd month (P = 0.001). Area under receiver operating characteristic curve for determining the 3 rd month virological response by baseline HBV DNA was 77.6% (95% CI: 66.7-85.2%), with a best cut-off value of 5.8 log 10 . Baseline HBV DNA, HBeAg negativity, and ALT were independent factors contributing to virological response at the 3 rd month. Further, multiple regression showed that HBV DNA level was the only parameter predicting full virological response as early as the 3 rd month, in this cirrhosis cohort.

  16. Predicting the outcome of ankylosing spondylitis therapy.

    Science.gov (United States)

    Vastesaeger, Nathan; van der Heijde, Désirée; Inman, Robert D; Wang, Yanxin; Deodhar, Atul; Hsu, Benjamin; Rahman, Mahboob U; Dijkmans, Ben; Geusens, Piet; Vander Cruyssen, Bert; Collantes, Eduardo; Sieper, Joachim; Braun, Jürgen

    2011-06-01

    To create a model that provides a potential basis for candidate selection for anti-tumour necrosis factor (TNF) treatment by predicting future outcomes relative to the current disease profile of individual patients with ankylosing spondylitis (AS). ASSERT and GO-RAISE trial data (n=635) were analysed to identify baseline predictors for various disease-state and disease-activity outcome instruments in AS. Univariate, multivariate, receiver operator characteristic and correlation analyses were performed to select final predictors. Their associations with outcomes were explored. Matrix and algorithm-based prediction models were created using logistic and linear regression, and their accuracies were compared. Numbers needed to treat were calculated to compare the effect size of anti-TNF therapy between the AS matrix subpopulations. Data from registry populations were applied to study how a daily practice AS population is distributed over the prediction model. Age, Bath ankylosing spondylitis functional index (BASFI) score, enthesitis, therapy, C-reactive protein (CRP) and HLA-B27 genotype were identified as predictors. Their associations with each outcome instrument varied. However, the combination of these factors enabled adequate prediction of each outcome studied. The matrix model predicted outcomes as well as algorithm-based models and enabled direct comparison of the effect size of anti-TNF treatment outcome in various subpopulations. The trial populations reflected the daily practice AS population. Age, BASFI, enthesitis, therapy, CRP and HLA-B27 were associated with outcomes in AS. Their combined use enables adequate prediction of outcome resulting from anti-TNF and conventional therapy in various AS subpopulations. This may help guide clinicians in making treatment decisions in daily practice.

  17. A somatization comorbidity phenotype impacts response to therapy in rheumatoid arthritis: post-hoc results from the certolizumab pegol phase 4 PREDICT trial.

    Science.gov (United States)

    Curtis, Jeffrey R; Herrem, Christopher; Ndlovu, 'Matladi N; O'Brien, Cathy; Yazici, Yusuf

    2017-09-29

    Comorbidities may contribute to disease activity and treatment response in rheumatoid arthritis (RA) patients. We defined a somatization comorbidity phenotype (SCP) and examined its influence on response to certolizumab pegol (CZP) using data from the PREDICT trial. Patients in PREDICT were randomized to the patient-reported Routine Assessment of Patient Index Data 3 (RAPID3) or physician-based Clinical Disease Activity Index (CDAI) for treatment response assessment. Post-hoc analyses identified patients with the SCP, which included diagnosis of depression, fibromyalgia/myalgias, and/or use of medications indicated for treatment of depression, anxiety, or neuropathic pain. The effect of the SCP on RAPID3 or CDAI response at week 12 and low disease activity (LDA; Disease Activity Score in 28 joints based on erythrocyte sedimentation rate ≤ 3.2) at week 52, in week-12 responders, was analyzed using non-parametric analysis of covariance (ANCOVA). At baseline, 43% (313/733) of patients met the SCP classification. Patients with the SCP were 9% more likely to withdraw from the trial. American College of Rheumatology 20% (ACR20), ACR50, and ACR70 responses were 5-14% lower among those with the SCP, and 11% more patients reported adverse events (AEs). Patients without SCP in the CDAI arm were twice as likely to achieve LDA at week 52 compared with those with SCP (32% versus 16%). No differentiation by SCP was observed in the RAPID3 arm (pooled result 21.5%). We operationalized a potentially important somatization comorbidity phenotype in a trial setting that was associated with a substantially lower likelihood of treatment response and a higher frequency of AEs. Including large numbers of patients with this phenotype in RA trials may reduce the measured clinical effectiveness of a new molecule. ClinicalTrials.gov, NCT01255761 . Registered on 6 December 2010.

  18. Predictive Factor Analysis of Response-Adapted Radiation Therapy for Chemotherapy-Sensitive Pediatric Hodgkin Lymphoma: Analysis of the Children's Oncology Group AHOD 0031 Trial

    Energy Technology Data Exchange (ETDEWEB)

    Charpentier, Anne-Marie [Department of Radiation Oncology, Centre hospitalier de l' Université de Montréal, Montreal, Québec (Canada); Friedman, Debra L. [Department of Pediatrics, Vanderbilt University School of Medicine, Nashville, Tennessee (United States); Wolden, Suzanne [Radiation Oncology, Memorial Sloan-Kettering Cancer Center, New York, New York (United States); Schwartz, Cindy [Division of Pediatrics, The University of Texas MD Anderson Cancer Center, Houston, Texas (United States); Gill, Bethany; Sykes, Jenna; Albert-Green, Alisha [Biostatistics, Princess Margaret Cancer Centre, University Health Network, Toronto, Ontario (Canada); Kelly, Kara M. [Division of Hematology and Oncology, Women & Children' s Hospital of Buffalo, Buffalo, New York (United States); Department of Pediatrics, Roswell Park Cancer Institute, Buffalo, New York (United States); Constine, Louis S. [Radiation Oncology, University of Rochester Medical Center, Rochester, New York (United States); Hodgson, David C., E-mail: David.hodgson@rmp.uhn.on.ca [Radiation Medicine Program, Princess Margaret Cancer Centre, University of Toronto, Toronto, Ontario (Canada)

    2016-12-01

    Purpose: To evaluate whether clinical risk factors could further distinguish children with intermediate-risk Hodgkin lymphoma (HL) with rapid early and complete anatomic response (RER/CR) who benefit significantly from involved-field RT (IFRT) from those who do not, and thereby aid refinement of treatment selection. Methods and Materials: Children with intermediate-risk HL treated on the Children's Oncology Group AHOD 0031 trial who achieved RER/CR with 4 cycles of chemotherapy, and who were randomized to 21-Gy IFRT or no additional therapy (n=716) were the subject of this study. Recursive partitioning analysis was used to identify factors associated with clinically and statistically significant improvement in event-free survival (EFS) after randomization to IFRT. Bootstrap sampling was used to evaluate the robustness of the findings. Result: Although most RER/CR patients did not benefit significantly from IFRT, those with a combination of anemia and bulky limited-stage disease (n=190) had significantly better 4-year EFS with the addition of IFRT (89.3% vs 77.9% without IFRT; P=.019); this benefit was consistently reproduced in bootstrap analyses and after adjusting for other prognostic factors. Conclusion: Although most patients achieving RER/CR had favorable outcomes with 4 cycles of chemotherapy alone, those children with initial bulky stage I/II disease and anemia had significantly better EFS with the addition of IFRT as part of combined-modality therapy. Further work evaluating the interaction of clinical and biologic factors and imaging response is needed to further optimize and refine treatment selection.

  19. Non-cardiac factors for prediction of response to cardiac resynchronization therapy: The value of baseline, and of serial changes, in red cell distribution width.

    Science.gov (United States)

    Carluccio, Erberto; Biagioli, Paolo; Alunni, Gianfranco; Murrone, Adriano; Zingarini, Gianluca; Coiro, Stefano; D'Antonio, Antonella; Mengoni, Anna; Cerasa, Maria Francesca; Ambrosio, Giuseppe

    2017-09-15

    Increased red blood cell distribution width (RDW) has been associated with poor outcome after cardiac resynchronization therapy (CRT). However, whether baseline RDW, and its serial changes after CRT implant, have incremental prognostic value is unknown. In 148 consecutive patients (age, 68±9years; 122 men) undergoing CRT, RDW was assessed before and 3months after implant. Patients were categorized according to baseline RDW (≤14.5% vs >14.5%); and as "stable", "decreased", "increased", relative to post-implant changes. Primary end-point was a composite of death/HF hospitalization during follow-up (median 21months). A reduction in left ventricular (LV) end-systolic volume by ≥15% at 6-month identified LV reverse remodeling. By multivariable logistic regression analysis "increased" (OR:0.22, 95%CI: 0.07-0.69, P=0.010) and "stable-high" RDW at follow-up (OR: 0.39, 95%CI: 0.17-0.89, P=0.027) showed a lower likelihood to develop LV reverse remodeling, while baseline RDW was no longer predictive of LV remodeling. During follow-up, there were 57 events. Baseline RDW>14.5% (HR: 2.24, 95%CI: 1.05-4.77, P=0.036), "increased" (HR: 2.55, 95% CI: 1.09-5.97, P=0.030) and "stable-high" RDW (HR: 2.95, 95% CI: 1.45-5.99, P=0.003) independently predicted outcome after adjusting for functional improvement after CRT, radial dyssynchrony, BNP, creatinine clearance, and left atrial volume index. However, integrated discrimination improvement and net reclassification improvement were not statistically significant when both baseline RDW and its changes were added to a base predictive model. Increased and stable-high values of RDW were independently associated with both LV reverse remodeling and outcome after CRT; however, RDW did not show any incremental predictive value. Copyright © 2017 Elsevier B.V. All rights reserved.

  20. A review of immune therapy in cancer and a question: can thermal therapy increase tumor response?

    Science.gov (United States)

    Bull, Joan M C

    2017-11-03

    Immune therapy is a successful cancer treatment coming into its own. This is because checkpoint molecules, adoptive specific lymphocyte transfer and chimeric antigen T-cell (CAR-T) therapy are able to induce more durable responses in an increasing number of malignancies compared to chemotherapy. In addition, immune therapies are able to treat bulky disease, whereas standard cytotoxic therapies cannot treat large tumour burdens. Checkpoint inhibitor monoclonal antibodies are becoming widely used in the clinic and although more complex, adoptive lymphocyte transfer and CAR-T therapies show promise. We are learning that there are nuances to predicting the successful use of the checkpoint inhibitors as well as to specific-antigen adoptive and CAR-T therapies. We are also newly aware of a here-to-fore unrealised natural force, the status of the microbiome. However, despite better understanding of mechanisms of action of the new immune therapies, the best responses to the new immune therapies remain 20-30%. Likely the best way to improve this somewhat low response rate for patients is to increase the patient's own immune response. Thermal therapy is a way to do this. All forms of thermal therapy, from fever-range systemic thermal therapy, to high-temperature HIFU and even cryotherapy improve the immune response pre-clinically. It is time to test the immune therapies with thermal therapy in vivo to test for optimal timing of the combinations that will best enhance tumour response and then to begin to test the immune therapies with thermal therapy in the clinic as soon as possible.

  1. The role of baseline Ga-68 DOTATATE positron emission tomography/computed tomography in the prediction of response to fixed-dose peptide receptor radionuclide therapy with Lu-177 DOTATATE.

    Science.gov (United States)

    Soydal, Çiğdem; Peker, Ahmet; Özkan, Elgin; Küçük, Özlem Nuriye; Kir, Metin Kemal

    2016-02-17

    To describe the role of baseline gallium (Ga)-68 DOTATATE positron emission tomography (PET)/computed tomography (CT) in the prediction of the response to peptide receptor radionuclide therapy (PRRT) using lutetium (Lu)-177 DOTATATE. Analysis was made of baseline Ga-68 DOTATATE PET/CT images of 29 patients (17 females and 12 males; mean age: 50.7 ± 14.6 years) with metastatic neuroendocrine tumors who received PRRT with Lu-177 DOTATATE. Maximum standardized uptake values (SUVmax) of reference lesions and their ratios to physiological uptake organs were calculated. The relationship between these values and the radiological response was analyzed. Partial response was observed in 8 (28%) patients, stable disease in 18 (62%) patients, and progressive disease in 3 (10%) patients. Mean SUVmax of reference lesions was calculated as 23.8 ± 20.5 (min-max: 5.1-87.3). There was no significant correlation between radiological responses and SUVmax of reference lesions and their ratios to other organs. Baseline Ga-68 DOTATATE PET/CT helps to show somatostatin receptor expression status and disease stage in patients who are candidates for PRRT. However, SUVs do not have a role in the prediction of treatment response.

  2. High Current CD4+ T Cell Count Predicts Suboptimal Adherence to Antiretroviral Therapy

    NARCIS (Netherlands)

    Pasternak, Alexander O.; de Bruin, Marijn; Bakker, Margreet; Berkhout, Ben; Prins, Jan M.

    2015-01-01

    High levels of adherence to antiretroviral therapy (ART) are necessary for achieving and maintaining optimal virological suppression, as suboptimal adherence leads to therapy failure and disease progression. It is well known that adherence to ART predicts therapy response, but it is unclear whether

  3. High current CD4+ T cell count predicts suboptimal adherence to antiretroviral therapy

    NARCIS (Netherlands)

    Pasternak, A.O.; de Bruin, M.; Bakker, M.; Berkhout, B.; Prins, J.M.

    2015-01-01

    High levels of adherence to antiretroviral therapy (ART) are necessary for achieving and maintaining optimal virological suppression, as suboptimal adherence leads to therapy failure and disease progression. It is well known that adherence to ART predicts therapy response, but it is unclear whether

  4. Predicting Treatment Response of Colorectal Cancer Liver Metastases to Conventional Lipiodol-Based Transarterial Chemoembolization Using Diffusion-Weighted MR Imaging: Value of Pretreatment Apparent Diffusion Coefficients (ADC) and ADC Changes Under Therapy

    Energy Technology Data Exchange (ETDEWEB)

    Lahrsow, Maximilian, E-mail: mlahrsow@gmail.com; Albrecht, Moritz H. [University Hospital Frankfurt, Department of Diagnostic and Interventional Radiology (Germany); Bickford, Matthew W. [Medical University of South Carolina, Department of Radiology and Radiological Science (United States); Vogl, Thomas J. [University Hospital Frankfurt, Department of Diagnostic and Interventional Radiology (Germany)

    2017-06-15

    PurposeTo use absolute pretreatment apparent diffusion coefficients (ADC) derived from diffusion-weighted MR imaging (DWI) to predict response to repetitive cTACE for unresectable liver metastases of colorectal carcinoma (CRLM) at 1 and 3 months after start of treatment.Materials and MethodsFifty-five metastases in 34 patients were examined with DWI prior to treatment and 1 month after initial cTACE. Treatment was performed in 4-week intervals. Response was evaluated at 1 and 3 months after start of therapy. Metastases showing a decrease of ≥30% in axial diameter were classified as responding lesions.ResultsOne month after initial cTACE, seven lesions showed early response. There was no significant difference in absolute pretreatment ADC values between responding and non-responding lesions (p = 0.94). Three months after initial cTACE, 17 metastases showed response. There was a significant difference (p = 0.021) between absolute pretreatment ADC values of lesions showing response (median 1.08 × 10{sup −3} mm{sup 2}/s) and no response (median 1.30 × 10{sup −3} mm{sup 2}/s). Pretreatment ADC showed fair diagnostic value to predict response (AUC 0.7). Lesions showing response at 3 months also revealed a significant increase in ADC between measurements before treatment and at one month after initial cTACE (p < 0.001). Applying an increase in ADC of 12.17%, response at 3 months after initial cTACE could be predicted with a sensitivity and specificity of 77 and 74%, respectively (AUC 0.817). Furthermore, there was a strong and significant correlation (r = 0.651, p < 0.001) between percentage change in size after third cTACE and percentage change in ADC.ConclusionIn patients with CRLM, ADC measurements are potential biomarkers for assessing response to cTACE.

  5. Positron emission tomography response at the time of autologous stem cell transplantation predicts outcome of patients with relapsed and/or refractory Hodgkin's lymphoma responding to prior salvage therapy.

    Science.gov (United States)

    Devillier, Raynier; Coso, Diane; Castagna, Luca; Brenot Rossi, Isabelle; Anastasia, Antonella; Chiti, Arturo; Ivanov, Vadim; Schiano, Jean Marc; Santoro, Armando; Chabannon, Christian; Balzarotti, Monica; Blaise, Didier; Bouabdallah, Reda

    2012-07-01

    High-dose chemotherapy followed by autologous stem cell transplantation is the standard treatment for relapsed and/or refractory Hodgkin's lymphoma although half of patients relapse after transplantation. Predictive factors, such as relapse within 12 months, Ann-Arbor stage at relapse, and relapse in previously irradiated fields are classically used to identify patients with poor outcome. Recently, 18-fluorodeoxyglucose positron emission tomography has emerged as a new method for providing information to predict outcome. The aim of this study was to confirm the predictive value of positron emission tomography status after salvage therapy and to compare single versus tandem autologous stem cell transplantation in patients with relapsed and/or refractory Hodgkin's lymphoma. We report a series of 111 consecutive patients with treatment-sensitive relapsed and/or treatment-refractory Hodgkin's lymphoma who achieved complete (positron emission tomography-negative group) or partial remission (positron emission tomography-positive group) at positron emission tomography evaluation after salvage chemotherapy and who underwent single or tandem autologous stem cell transplantation. Five-year overall and progression-free survival rates were 81% and 64%, respectively. There were significant differences in 5-year progression-free survival (79% versus 23%; P<0.001) and 5-year overall survival (90% versus 55%, P=0.001) between the positron emission tomography-negative and -positive groups, respectively. A complete response, as determined by positron emission tomography evaluation, after salvage therapy predicted significantly better 5-year overall survival rates in both intermediate (91% versus 50%; P=0.029) and unfavorable (89% versus 58%; P=0.026) risk subgroup analyses. In the positron emission tomography-positive subgroup, tandem transplantation improved 5-year progression-free survival from 0% (in the single transplantation group) to 43% (P=0.034). Multivariate analysis showed

  6. Positron emission tomography response at the time of autologous stem cell transplantation predicts outcome of patients with relapsed and/or refractory Hodgkin’s lymphoma responding to prior salvage therapy

    Science.gov (United States)

    Devillier, Raynier; Coso, Diane; Castagna, Luca; Brenot Rossi, Isabelle; Anastasia, Antonella; Chiti, Arturo; Ivanov, Vadim; Schiano, Jean Marc; Santoro, Armando; Chabannon, Christian; Balzarotti, Monica; Blaise, Didier; Bouabdallah, Reda

    2012-01-01

    Background High-dose chemotherapy followed by autologous stem cell transplantation is the standard treatment for relapsed and/or refractory Hodgkin’s lymphoma although half of patients relapse after transplantation. Predictive factors, such as relapse within 12 months, Ann-Arbor stage at relapse, and relapse in previously irradiated fields are classically used to identify patients with poor outcome. Recently, 18-fluorodeoxyglucose positron emission tomography has emerged as a new method for providing information to predict outcome. The aim of this study was to confirm the predictive value of positron emission tomography status after salvage therapy and to compare single versus tandem autologous stem cell transplantation in patients with relapsed and/or refractory Hodgkin’s lymphoma. Design and Methods We report a series of 111 consecutive patients with treatment-sensitive relapsed and/or treatment-refractory Hodgkin’s lymphoma who achieved complete (positron emission tomography-negative group) or partial remission (positron emission tomography-positive group) at positron emission tomography evaluation after salvage chemotherapy and who underwent single or tandem autologous stem cell transplantation. Results Five-year overall and progression-free survival rates were 81% and 64%, respectively. There were significant differences in 5-year progression-free survival (79% versus 23%; P<0.001) and 5-year overall survival (90% versus 55%, P=0.001) between the positron emission tomography-negative and -positive groups, respectively. A complete response, as determined by positron emission tomography evaluation, after salvage therapy predicted significantly better 5-year overall survival rates in both intermediate (91% versus 50%; P=0.029) and unfavorable (89% versus 58%; P=0.026) risk subgroup analyses. In the positron emission tomography-positive subgroup, tandem transplantation improved 5-year progression-free survival from 0% (in the single transplantation group) to

  7. Drug response prediction in high-risk multiple myeloma

    DEFF Research Database (Denmark)

    Vangsted, A J; Helm-Petersen, S; Cowland, J B

    2018-01-01

    A Drug Response Prediction (DRP) score was developed based on gene expression profiling (GEP) from cell lines and tumor samples. Twenty percent of high-risk patients by GEP70 treated in Total Therapy 2 and 3A have a progression-free survival (PFS) of more than 10years. We used available GEP data ...

  8. Response to cardiac resynchronization therapy

    DEFF Research Database (Denmark)

    Versteeg, Henneke; Schiffer, Angélique A; Widdershoven, Jos W

    2009-01-01

    Cardiac resynchronization therapy (CRT) is a promising treatment for a subgroup of patients with advanced congestive heart failure and a prolonged QRS interval. Despite the majority of patients benefiting from CRT, 10-40% of patients do not respond to this treatment and are labeled as nonresponders...

  9. Pretreatment Prediction of Individual Rheumatoid Arthritis Patients' Response to Anti-Cytokine Therapy Using Serum Cytokine/Chemokine/Soluble Receptor Biomarkers: e0132055

    National Research Council Canada - National Science Library

    Kazuko Uno; Kazuyuki Yoshizaki; Mitsuhiro Iwahashi; Jiro Yamana; Seizo Yamana; Miki Tanigawa; Katsumi Yagi

    2015-01-01

      The inability to match rheumatoid arthritis (RA) patients with the anti-cytokine agent most efficacious for them is a major hindrance to patients' speedy recovery and to the clinical use of anti-cytokine therapy...

  10. Has the degree of contrast enhancement with MR imaging in laryngeal carcinoma added value to Anatomic parameters regarding prediction of response to radiation therapy?

    NARCIS (Netherlands)

    Ljumanovic, R.; Pouwels, P. J. W.; Langendijk, J. A.; Knol, D. L.; Van der Valk, P.; Leemans, C. R.; Castelijns, J. A.

    BACKGROUND AND PURPOSE: Our aim was to retrospectively investigate the prognostic significance of the degree of contrast enhancement in tumors and its additional value in previously considered MR imaging parameters with regard to local control of laryngeal cancer treated with radiation therapy (RT)

  11. Neither Baseline nor Changes in Serum Triiodothyronine during Levothyroxine/Liothyronine Combination Therapy Predict a Positive Response to This Treatment Modality in Hypothyroid Patients with Persistent Symptoms

    DEFF Research Database (Denmark)

    Medici, Bjarke Borregaard; la Cour, Jeppe Lerche; Michaelsson, Luba Freja

    2017-01-01

    BACKGROUND: Despite biochemical euthyroidism, some levothyroxine (L-T4)-treated hypothyroid patients report persisting symptoms and some of these patients are tentatively treated with a combination of L-T4 and liothyronine (L-T3). Combination therapy and the appropriate choice of blood tests...

  12. FDG-PET response-adapted therapy

    DEFF Research Database (Denmark)

    Hutchings, Martin

    2014-01-01

    Fluorodeoxyglucose (FDG) positron emission tomography (PET)/computed tomography (CT) is the most accurate tool for staging, treatment monitoring, and response evaluation in Hodgkin lymphoma (HL). Early determination of treatment sensitivity by FDG-PET is the best tool to guide individualized......, response-adapted treatment. Several ongoing or recently completed trials have investigated the use of FDG-PET/CT for early response-adapted HL therapy. The results are encouraging, but the data are immature, and PET response-adapted HL therapy is discouraged outside the setting of clinical trials. PET...

  13. Imaging Neoadjuvant Therapy Response in Breast Cancer.

    Science.gov (United States)

    Fowler, Amy M; Mankoff, David A; Joe, Bonnie N

    2017-11-01

    The use of neoadjuvant systemic therapy in the treatment of breast cancer patients is increasing beyond the scope of locally advanced disease. Imaging provides important information in assessing response to therapy as a complement to conventional tumor measurements via physical examination. The purpose of this article is to discuss the advantages and limitations of current assessment methods, as well as review functional and molecular imaging approaches being investigated as emerging techniques for evaluating neoadjuvant therapy response for patients with primary breast cancer. (©) RSNA, 2017.

  14. Metabolomic profiling predicts outcome of rituximab therapy in rheumatoid arthritis

    Science.gov (United States)

    Sweeney, Shannon R; Kavanaugh, Arthur; Lodi, Alessia; Wang, Bo; Boyle, David; Tiziani, Stefano; Guma, Monica

    2016-01-01

    Objective: To determine whether characterisation of patients' metabolic profiles, utilising nuclear magnetic resonance (NMR) and mass spectrometry (MS), could predict response to rituximab therapy. 23 patients with active, seropositive rheumatoid arthritis (RA) on concomitant methotrexate were treated with rituximab. Patients were grouped into responders and non-responders according to the American College of Rheumatology improvement criteria, at a 20% level at 6 months. A Bruker Avance 700 MHz spectrometer and a Thermo Scientific Q Exactive Hybrid Quadrupole-Orbitrap mass spectrometer were used to acquire 1H-NMR and ultra high pressure liquid chromatography (UPLC)–MS/MS spectra, respectively, of serum samples before and after rituximab therapy. Data processing and statistical analysis were performed in MATLAB. 14 patients were characterised as responders, and 9 patients were considered non-responders. 7 polar metabolites (phenylalanine, 2-hydroxyvalerate, succinate, choline, glycine, acetoacetate and tyrosine) and 15 lipid species were different between responders and non-responders at baseline. Phosphatidylethanolamines, phosphatidyserines and phosphatidylglycerols were downregulated in responders. An opposite trend was observed in phosphatidylinositols. At 6 months, 5 polar metabolites (succinate, taurine, lactate, pyruvate and aspartate) and 37 lipids were different between groups. The relationship between serum metabolic profiles and clinical response to rituximab suggests that 1H-NMR and UPLC–MS/MS may be promising tools for predicting response to rituximab. PMID:27651926

  15. Metabolomic profiling predicts outcome of rituximab therapy in rheumatoid arthritis.

    Science.gov (United States)

    Sweeney, Shannon R; Kavanaugh, Arthur; Lodi, Alessia; Wang, Bo; Boyle, David; Tiziani, Stefano; Guma, Monica

    2016-01-01

    To determine whether characterisation of patients' metabolic profiles, utilising nuclear magnetic resonance (NMR) and mass spectrometry (MS), could predict response to rituximab therapy. 23 patients with active, seropositive rheumatoid arthritis (RA) on concomitant methotrexate were treated with rituximab. Patients were grouped into responders and non-responders according to the American College of Rheumatology improvement criteria, at a 20% level at 6 months. A Bruker Avance 700 MHz spectrometer and a Thermo Scientific Q Exactive Hybrid Quadrupole-Orbitrap mass spectrometer were used to acquire (1)H-NMR and ultra high pressure liquid chromatography (UPLC)-MS/MS spectra, respectively, of serum samples before and after rituximab therapy. Data processing and statistical analysis were performed in MATLAB. 14 patients were characterised as responders, and 9 patients were considered non-responders. 7 polar metabolites (phenylalanine, 2-hydroxyvalerate, succinate, choline, glycine, acetoacetate and tyrosine) and 15 lipid species were different between responders and non-responders at baseline. Phosphatidylethanolamines, phosphatidyserines and phosphatidylglycerols were downregulated in responders. An opposite trend was observed in phosphatidylinositols. At 6 months, 5 polar metabolites (succinate, taurine, lactate, pyruvate and aspartate) and 37 lipids were different between groups. The relationship between serum metabolic profiles and clinical response to rituximab suggests that (1)H-NMR and UPLC-MS/MS may be promising tools for predicting response to rituximab.

  16. Predicting responses from Rasch measures.

    Science.gov (United States)

    Linacre, John M

    2010-01-01

    There is a growing family of Rasch models for polytomous observations. Selecting a suitable model for an existing dataset, estimating its parameters and evaluating its fit is now routine. Problems arise when the model parameters are to be estimated from the current data, but used to predict future data. In particular, ambiguities in the nature of the current data, or overfit of the model to the current dataset, may mean that better fit to the current data may lead to worse fit to future data. The predictive power of several Rasch and Rasch-related models are discussed in the context of the Netflix Prize. Rasch-related models are proposed based on Singular Value Decomposition (SVD) and Boltzmann Machines.

  17. Basal (18)F-FDG PET/CT as a predictive biomarker of tumor response for neoadjuvant therapy in breast cancer.

    Science.gov (United States)

    García Vicente, A M; Soriano Castrejón, A; Pruneda-González, R E; Fernández Calvo, G; Muñoz Sánchez, M M; Álvarez Cabellos, R; Espinosa Aunión, R; Relea Calatayud, F

    2016-01-01

    To explore the relation between tumor kinetic assessed by (18)F-FDG PET and final neoadjuvant chemotherapy (NC) response within a molecular phenotype perspective. Prospective study included 144 women with breast cancer. All patients underwent a dual-time point (18)F-FDG PET/CT previous to NC. The retention index (RI), between SUV-1 and SUV-2 was calculated. Molecular subtypes were re-grouped in low, intermediate and high-risk biological phenotypes. After NC, all residual primary tumor specimens were histopathologically classified in tumor regression grades (TRG) and response groups. The relation between SUV-1, SUV-2 and RI with the TRG and response groups was evaluated in all molecular subtypes and in accordance with the risk categories. Responder's lesions showed significant greater SUVmax compared to non-responders. The RI value did not show any significant relation with response. Attending to molecular phenotypes, statistical differences were observed with greater SUV for responders having high-risk molecular subtypes. Glycolytic tumor characteristics showed a significant correlation with NC response and dependence of risk phenotype. Copyright © 2015 Elsevier España, S.L.U. and SEMNIM. All rights reserved.

  18. Predictive value of pharmacokinetics-adjusted phenotypic susceptibility on response to ritonavir-enhanced protease inhibitors (PIs) in human immunodeficiency virus-infected subjects failing prior PI therapy.

    Science.gov (United States)

    Eron, Joseph J; Park, Jeong-Gun; Haubrich, Richard; Aweeka, Francesca; Bastow, Barbara; Pakes, Gary E; Yu, Song; Wu, Hulin; Richman, Douglas D

    2009-06-01

    The activities of protease inhibitors in vivo may depend on plasma concentrations and viral susceptibility. This nonrandomized, open-label study evaluated the relationship of the inhibitory quotient (IQ [the ratio of drug exposure to viral phenotypic susceptibility]) to the human immunodeficiency virus type 1 (HIV-1) viral load (VL) change for ritonavir-enhanced protease inhibitors (PIs). Subjects on PI-based regimens replaced their PIs with ritonavir-enhanced indinavir (IDV/r) 800/200 mg, fosamprenavir (FPV/r) 700/100 mg, or lopinavir (LPV/r) 400/200 mg twice daily. Pharmacokinetics were assessed at day 14; follow-up lasted 24 weeks. Associations between IQ and VL changes were examined. Fifty-three subjects enrolled, 12 on IDV/r, 33 on FPV/r, and 8 on LPV/r. Median changes (n-fold) (FC) of 50% inhibitory concentrations (IC(50)s) to the study PI were high. Median 2-week VL changes were -0.7, -0.1, and -1.0 log(10) for IDV/r, FPV/r, and LPV/r. With FPV/r, correlations between the IQ and the 2-week change in VL were significant (Spearman's r range, -0.39 to -0.50; P PI-experienced subjects with highly resistant HIV-1, short-term VL responses to RTV-enhanced FPV/r correlated best with baseline susceptibility. The IQ improved correlation in analyses of all arms where a greater range of virologic responses was observed.

  19.  DNA microarray-based gene expression profiling in diagnosis, assessing prognosis and predicting response to therapy in colorectal cancer

    Directory of Open Access Journals (Sweden)

    Przemysław Kwiatkowski

    2012-06-01

    Full Text Available  Colorectal cancer is the most common cancer of the gastrointestinal tract. It is considered as a biological model of a certain type of cancerogenesis process in which progression from an early to late stage adenoma and cancer is accompanied by distinct genetic alterations.Clinical and pathological parameters commonly used in clinical practice are often insufficient to determine groups of patients suitable for personalized treatment. Moreover, reliable molecular markers with high prognostic value have not yet been determined. Molecular studies using DNA-based microarrays have identified numerous genes involved in cell proliferation and differentiation during the process of cancerogenesis. Assessment of the genetic profile of colorectal cancer using the microarray technique might be a useful tool in determining the groups of patients with different clinical outcomes who would benefit from additional personalized treatment.The main objective of this study was to present the current state of knowledge on the practical application of gene profiling techniques using microarrays for determining diagnosis, prognosis and response to treatment in colorectal cancer.

  20. Prediction of treatment response to adalimumab

    DEFF Research Database (Denmark)

    Krintel, S. B.; Dehlendorff, C.; Hetland, M. L.

    2016-01-01

    At least 30% of patients with rheumatoid arthritis (RA) do not respond to biologic agents, which emphasizes the need of predictive biomarkers. We aimed to identify microRNAs (miRNAs) predictive of response to adalimumab in 180 treatment-naïve RA patients enrolled in the OPtimized treatment algori...... of low expression of miR-22 and high expression of miR-886.3p was associated with EULAR good response. Future studies to assess the utility of these miRNAs as predictive biomarkers are needed.The Pharmacogenomics Journal advance online publication, 5 May 2015; doi:10.1038/tpj.2015.30....

  1. Menopausal estrogen therapy predicts better nocturnal oxyhemoglobin saturation.

    Science.gov (United States)

    Saaresranta, Tarja; Polo-Kantola, Päivi; Virtanen, Irina; Vahlberg, Tero; Irjala, Kerttu; Polo, Olli

    2006-10-20

    The respiratory responses in the few previous studies evaluating the effects of short-term unopposed estrogen therapy on breathing in postmenopausal women have been inconsistent. We performed a study to investigate whether long-term estrogen therapy would prevent age-related decline in nocturnal arterial oxyhemoglobin saturation and whether higher serum estradiol concentration is associated with better arterial oxyhemoglobin saturation. Sixty-four healthy postmenopausal women were followed-up for 5 years in a 5-year prospective open follow-up study. The women were users or non-users of estrogen therapy according to their personal preference. Mean overnight arterial oxyhemoglobin saturation was similar at baseline (94.3 +/- 1.1%) and after follow-up (94.5 +/- 1.6%). Present estrogen users had higher mean arterial oxyhemoglobin saturation (95.2 +/- 1.4%) than present non-users (94.0 +/- 1.5%), when adjusted for age and body mass index (p = 0.042). The change in mean arterial oxyhemoglobin saturation during follow-up was not associated with serum estradiol concentration at baseline but associated with estradiol at follow-up (p = 0.042), when adjusted for age and body mass index. At follow-up, women with higher serum estradiol concentration had also higher mean nocturnal arterial oxyhemoglobin saturation (Pearson r = 0.29, p = 0.019) and lower apnea-hypopnea index (Spearman r = -0.28, p = 0.031). The pooled current estrogen users spent proportionally less time with SaO(2) below 90% than non-users (ANCOVA adjusted for age and BMI, p = 0.017). Estrogen use and especially high serum estradiol concentration predict higher mean overnight arterial oxyhemoglobin saturation. The present data suggest that estrogen therapy has favorable respiratory effects.

  2. Response predictions using the observed autocorrelation function

    DEFF Research Database (Denmark)

    Nielsen, Ulrik Dam; H. Brodtkorb, Astrid; Jensen, Jørgen Juncher

    2018-01-01

    This article studies a procedure that facilitates short-time, deterministic predictions of the wave-induced motion of a marine vessel, where it is understood that the future motion of the vessel is calculated ahead of time. Such predictions are valuable to assist in the execution of many marine......-induced response in study. Thus, predicted (future) values ahead of time for a given time history recording are computed through a mathematical combination of the sample autocorrelation function and previous measurements recorded just prior to the moment of action. Importantly, the procedure does not need input...

  3. Predicting and measuring fluid responsiveness with echocardiography

    Directory of Open Access Journals (Sweden)

    Ashley Miller

    2016-06-01

    Full Text Available Echocardiography is ideally suited to guide fluid resuscitation in critically ill patients. It can be used to assess fluid responsiveness by looking at the left ventricle, aortic outflow, inferior vena cava and right ventricle. Static measurements and dynamic variables based on heart–lung interactions all combine to predict and measure fluid responsiveness and assess response to intravenous fluid esuscitation. Thorough knowledge of these variables, the physiology behind them and the pitfalls in their use allows the echocardiographer to confidently assess these patients and in combination with clinical judgement manage them appropriately.

  4. Prediction Models for Dynamic Demand Response

    Energy Technology Data Exchange (ETDEWEB)

    Aman, Saima; Frincu, Marc; Chelmis, Charalampos; Noor, Muhammad; Simmhan, Yogesh; Prasanna, Viktor K.

    2015-11-02

    As Smart Grids move closer to dynamic curtailment programs, Demand Response (DR) events will become necessary not only on fixed time intervals and weekdays predetermined by static policies, but also during changing decision periods and weekends to react to real-time demand signals. Unique challenges arise in this context vis-a-vis demand prediction and curtailment estimation and the transformation of such tasks into an automated, efficient dynamic demand response (D2R) process. While existing work has concentrated on increasing the accuracy of prediction models for DR, there is a lack of studies for prediction models for D2R, which we address in this paper. Our first contribution is the formal definition of D2R, and the description of its challenges and requirements. Our second contribution is a feasibility analysis of very-short-term prediction of electricity consumption for D2R over a diverse, large-scale dataset that includes both small residential customers and large buildings. Our third, and major contribution is a set of insights into the predictability of electricity consumption in the context of D2R. Specifically, we focus on prediction models that can operate at a very small data granularity (here 15-min intervals), for both weekdays and weekends - all conditions that characterize scenarios for D2R. We find that short-term time series and simple averaging models used by Independent Service Operators and utilities achieve superior prediction accuracy. We also observe that workdays are more predictable than weekends and holiday. Also, smaller customers have large variation in consumption and are less predictable than larger buildings. Key implications of our findings are that better models are required for small customers and for non-workdays, both of which are critical for D2R. Also, prediction models require just few days’ worth of data indicating that small amounts of

  5. Prediction of Drug Therapy for Chronic Hepatitis C Depending on the IL28B Gene Polymorphism

    Directory of Open Access Journals (Sweden)

    Moroz L.V. Moroz L.V.

    2014-09-01

    Molecular and genetic analysis of IL28V (rs12979860 gene polymorphism, located at a distance of 3 thousand nucleotide pairs from IL28V gene, using the polymerase chain reaction allows to predict the success of combination antiviral therapy, and the presence of C/C genotype can be a predictor of sustained virological response in patients chronic hepatitis C.

  6. Using Conversation Topics for Predicting Therapy Outcomes in Schizophrenia

    Science.gov (United States)

    Howes, Christine; Purver, Matthew; McCabe, Rose

    2013-01-01

    Previous research shows that aspects of doctor-patient communication in therapy can predict patient symptoms, satisfaction and future adherence to treatment (a significant problem with conditions such as schizophrenia). However, automatic prediction has so far shown success only when based on low-level lexical features, and it is unclear how well these can generalize to new data, or whether their effectiveness is due to their capturing aspects of style, structure or content. Here, we examine the use of topic as a higher-level measure of content, more likely to generalize and to have more explanatory power. Investigations show that while topics predict some important factors such as patient satisfaction and ratings of therapy quality, they lack the full predictive power of lower-level features. For some factors, unsupervised methods produce models comparable to manual annotation. PMID:23943658

  7. Angiotensinogen and HLA class II predict bevacizumab response in recurrent glioblastoma patients

    DEFF Research Database (Denmark)

    Urup, Thomas; Michaelsen, Signe Regner; Olsen, Lars Rønn

    2016-01-01

    .0009) and high expression of a HLA class II gene (2-fold increase in HLA-DQA1; OR = 1.22; 95% CI: 1.01-1.47; P = 0.04). These two genes were included in a model that is able predict response to bevacizumab combination therapy in clinical practice. When stratified for a validated prognostic index, the predictive...... model for response was significantly associated with improved overall survival. Conclusion: Two genes (low angiotensinogen and high HLA-class II expression) were predictive for bevacizumab response and were included in a predictive model for response. This model can be used in clinical practice...... for bevacizumab response in recurrent glioblastoma patients. Methods: The study included a total of 82 recurrent glioblastoma patients treated with bevacizumab combination therapy whom were both response and biomarker evaluable. Gene expression of tumor tissue was analyzed by using a customized Nano...

  8. Gene-expression profiling to predict responsiveness to immunotherapy.

    Science.gov (United States)

    Jamieson, N B; Maker, A V

    2017-03-01

    Recent clinical successes with immunotherapy have resulted in expanding indications for cancer therapy. To enhance antitumor immune responses, and to better choose specific strategies matched to patient and tumor characteristics, genomic-driven precision immunotherapy will be necessary. Herein, we explore the role that tumor gene-expression profiling (GEP) may have in the prediction of an immunotherapeutic response. Genetic markers associated with response to immunotherapy are addressed as they pertain to the tumor genomic landscape, the extent of DNA damage, tumor mutational load and tumor-specific neoantigens. Furthermore, genetic markers associated with resistance to checkpoint blockade and relapse are reviewed. Finally, the utility of GEP to identify new tumor types for immunotherapy and implications for combinatorial strategies are summarized.

  9. Clinical predictive factors of pathologic tumor response

    Energy Technology Data Exchange (ETDEWEB)

    Choi, Chi Hwan; Kim, Won Dong; Lee, Sang Jeon; Park, Woo Yoon [Chungbuk National University College of Medicine, Cheongju (Korea, Republic of)

    2012-09-15

    The aim of this study was to identify clinical predictive factors for tumor response after preoperative chemoradiotherapy (CRT) in rectal cancer. The study involved 51 patients who underwent preoperative CRT followed by surgery between January 2005 and February 2012. Radiotherapy was delivered to the whole pelvis at a dose of 45 Gy in 25 fractions, followed by a boost of 5.4 Gy in 3 fractions to the primary tumor with 5 fractions per week. Three different chemotherapy regimens were used. Tumor responses to preoperative CRT were assessed in terms of tumor downstaging and pathologic complete response (ypCR). Statistical analyses were performed to identify clinical factors associated with pathologic tumor response. Tumor downstaging was observed in 28 patients (54.9%), whereas ypCR was observed in 6 patients (11.8%). Multivariate analysis found that predictors of downstaging was pretreatment relative lymphocyte count (p = 0.023) and that none of clinical factors was significantly associated with ypCR. Pretreatment relative lymphocyte count (%) has a significant impact on the pathologic tumor response (tumor downstaging) after preoperative CRT for locally advanced rectal cancer. Enhancement of lymphocyte-mediated immune reactions may improve the effect of preoperative CRT for rectal cancer.

  10. MTR-18 Predictive Biomarkers Of Bevacizumab Response In Recurrent Glioblastoma Patients

    DEFF Research Database (Denmark)

    Urup, Thomas; Michaelsen, Signe Regner; Olsen, Lars Rønn

    2015-01-01

    with the proneural GBM subtype have a survival benefit when treated with BEV in combination with standard treatment. However, no validated biomarkers able to predict BEV response have been identified and the biology reflecting a clinical BEV response is poorly understood. The primary objective of this study...... was to evaluate the predictive and prognostic value of GBM subtypes in recurrent GBM patients treated with BEV therapy. The secondary objective was to identify biomarkers able to predict response to BEV therapy in recurrent GBM patients. METHODS: A total of 90 recurrent GBM patients treated with BEV combination...... and multifocal disease. RESULTS: Molecular subtypes were not associated with response or survival. However, two independent predictive biomarkers (gene1 down-regulated and gene2 up-regulated in responders, respectively) of BEV response and survival were identified. Results will be presented....

  11. Prediction of psilocybin response in healthy volunteers.

    Science.gov (United States)

    Studerus, Erich; Gamma, Alex; Kometer, Michael; Vollenweider, Franz X

    2012-01-01

    Responses to hallucinogenic drugs, such as psilocybin, are believed to be critically dependent on the user's personality, current mood state, drug pre-experiences, expectancies, and social and environmental variables. However, little is known about the order of importance of these variables and their effect sizes in comparison to drug dose. Hence, this study investigated the effects of 24 predictor variables, including age, sex, education, personality traits, drug pre-experience, mental state before drug intake, experimental setting, and drug dose on the acute response to psilocybin. The analysis was based on the pooled data of 23 controlled experimental studies involving 409 psilocybin administrations to 261 healthy volunteers. Multiple linear mixed effects models were fitted for each of 15 response variables. Although drug dose was clearly the most important predictor for all measured response variables, several non-pharmacological variables significantly contributed to the effects of psilocybin. Specifically, having a high score in the personality trait of Absorption, being in an emotionally excitable and active state immediately before drug intake, and having experienced few psychological problems in past weeks were most strongly associated with pleasant and mystical-type experiences, whereas high Emotional Excitability, low age, and an experimental setting involving positron emission tomography most strongly predicted unpleasant and/or anxious reactions to psilocybin. The results confirm that non-pharmacological variables play an important role in the effects of psilocybin.

  12. Prediction of psilocybin response in healthy volunteers.

    Directory of Open Access Journals (Sweden)

    Erich Studerus

    Full Text Available Responses to hallucinogenic drugs, such as psilocybin, are believed to be critically dependent on the user's personality, current mood state, drug pre-experiences, expectancies, and social and environmental variables. However, little is known about the order of importance of these variables and their effect sizes in comparison to drug dose. Hence, this study investigated the effects of 24 predictor variables, including age, sex, education, personality traits, drug pre-experience, mental state before drug intake, experimental setting, and drug dose on the acute response to psilocybin. The analysis was based on the pooled data of 23 controlled experimental studies involving 409 psilocybin administrations to 261 healthy volunteers. Multiple linear mixed effects models were fitted for each of 15 response variables. Although drug dose was clearly the most important predictor for all measured response variables, several non-pharmacological variables significantly contributed to the effects of psilocybin. Specifically, having a high score in the personality trait of Absorption, being in an emotionally excitable and active state immediately before drug intake, and having experienced few psychological problems in past weeks were most strongly associated with pleasant and mystical-type experiences, whereas high Emotional Excitability, low age, and an experimental setting involving positron emission tomography most strongly predicted unpleasant and/or anxious reactions to psilocybin. The results confirm that non-pharmacological variables play an important role in the effects of psilocybin.

  13. Genetic Predictors of Response to Systemic Therapy in Esophagogastric Cancer.

    Science.gov (United States)

    Janjigian, Yelena Y; Sanchez-Vega, Francisco; Jonsson, Philip; Chatila, Walid K; Hechtman, Jaclyn F; Ku, Geoffrey Y; Riches, Jamie C; Tuvy, Yaelle; Kundra, Ritika; Bouvier, Nancy; Vakiani, Efsevia; Gao, Jianjiong; Heins, Zachary J; Gross, Benjamin E; Kelsen, David P; Zhang, Liying; Strong, Vivian E; Schattner, Mark; Gerdes, Hans; Coit, Daniel G; Bains, Manjit; Stadler, Zsofia K; Rusch, Valerie W; Jones, David R; Molena, Daniela; Shia, Jinru; Robson, Mark E; Capanu, Marinela; Middha, Sumit; Zehir, Ahmet; Hyman, David M; Scaltriti, Maurizio; Ladanyi, Marc; Rosen, Neal; Ilson, David H; Berger, Michael F; Tang, Laura; Taylor, Barry S; Solit, David B; Schultz, Nikolaus

    2018-01-01

    The incidence of esophagogastric cancer is rapidly rising, but only a minority of patients derive durable benefit from current therapies. Chemotherapy as well as anti-HER2 and PD-1 antibodies are standard treatments. To identify predictive biomarkers of drug sensitivity and mechanisms of resistance, we implemented prospective tumor sequencing of patients with metastatic esophagogastric cancer. There was no association between homologous recombination deficiency defects and response to platinum-based chemotherapy. Patients with microsatellite instability-high tumors were intrinsically resistant to chemotherapy but more likely to achieve durable responses to immunotherapy. The single Epstein-Barr virus-positive patient achieved a durable, complete response to immunotherapy. The level of ERBB2 amplification as determined by sequencing was predictive of trastuzumab benefit. Selection for a tumor subclone lacking ERBB2 amplification, deletion of ERBB2 exon 16, and comutations in the receptor tyrosine kinase, RAS, and PI3K pathways were associated with intrinsic and/or acquired trastuzumab resistance. Prospective genomic profiling can identify patients most likely to derive durable benefit to immunotherapy and trastuzumab and guide strategies to overcome drug resistance. Significance: Clinical application of multiplex sequencing can identify biomarkers of treatment response to contemporary systemic therapies in metastatic esophagogastric cancer. This large prospective analysis sheds light on the biological complexity and the dynamic nature of therapeutic resistance in metastatic esophagogastric cancers. Cancer Discov; 8(1); 49-58. ©2017 AACR. See related commentary by Sundar and Tan, p. 14 See related article by Pectasides et al., p. 37 This article is highlighted in the In This Issue feature, p. 1 . ©2017 American Association for Cancer Research.

  14. Predicting Change in Marital Satisfaction Throughout Emotionally Focused Couple Therapy.

    Science.gov (United States)

    Dalgleish, Tracy L; Johnson, Susan M; Burgess Moser, Melissa; Lafontaine, Marie-France; Wiebe, Stephanie A; Tasca, Giorgio A

    2015-07-01

    Emotionally focused couple therapy (EFT) is an empirically validated approach to couple therapy that uses attachment theory to understand the needs and emotions of romantic partners. EFT is recognized as one of the most effective approaches to couple therapy, but to guide therapists in their use of EFT, a theoretically based model to predict change is needed. This study tested such a model by recruiting 32 couples, and 14 therapists who provided approximately 21 sessions of EFT. Couples completed self-report measures of marital satisfaction, attachment security, relationship trust, and emotional control at pre- and posttherapy and after each therapy session. Results of hierarchical linear modeling suggested that individuals higher on self-report attachment anxiety and higher levels of emotional control had greater change in marital satisfaction across EFT sessions. Assessing attachment security at the start of therapy will inform therapists of the emotion regulating strategies used by couples and may help couples achieve positive outcomes from EFT. © 2014 American Association for Marriage and Family Therapy.

  15. Comparative Risk Predictions of Second Cancers After Carbon-Ion Therapy Versus Proton Therapy

    Energy Technology Data Exchange (ETDEWEB)

    Eley, John G., E-mail: jeley@som.umaryland.edu [Department of Radiation Physics, The University of Texas MD Anderson Cancer Center, Houston, Texas (United States); University of Texas Graduate School of Biomedical Sciences, Houston, Texas (United States); Department of Radiation Oncology, University of Maryland School of Medicine, Baltimore, Maryland (United States); Friedrich, Thomas [GSI Helmholtzzentrum für Schwerionenforschung GmbH, Darmstadt (Germany); Homann, Kenneth L.; Howell, Rebecca M. [Department of Radiation Physics, The University of Texas MD Anderson Cancer Center, Houston, Texas (United States); University of Texas Graduate School of Biomedical Sciences, Houston, Texas (United States); Scholz, Michael; Durante, Marco [GSI Helmholtzzentrum für Schwerionenforschung GmbH, Darmstadt (Germany); Newhauser, Wayne D. [Department of Physics and Astronomy, Louisiana State University and Agricultural and Mechanical College, Baton Rouge, Louisiana (United States); Mary Bird Perkins Cancer Center, Baton Rouge, Louisiana (United States)

    2016-05-01

    Purpose: This work proposes a theoretical framework that enables comparative risk predictions for second cancer incidence after particle beam therapy for different ion species for individual patients, accounting for differences in relative biological effectiveness (RBE) for the competing processes of tumor initiation and cell inactivation. Our working hypothesis was that use of carbon-ion therapy instead of proton therapy would show a difference in the predicted risk of second cancer incidence in the breast for a sample of Hodgkin lymphoma (HL) patients. Methods and Materials: We generated biologic treatment plans and calculated relative predicted risks of second cancer in the breast by using two proposed methods: a full model derived from the linear quadratic model and a simpler linear-no-threshold model. Results: For our reference calculation, we found the predicted risk of breast cancer incidence for carbon-ion plans-to-proton plan ratio, , to be 0.75 ± 0.07 but not significantly smaller than 1 (P=.180). Conclusions: Our findings suggest that second cancer risks are, on average, comparable between proton therapy and carbon-ion therapy.

  16. Can we predict the blood pressure response to renal denervation?

    Science.gov (United States)

    Fink, Gregory D; Phelps, Jeremiah T

    2017-05-01

    Renal denervation (RDN) is a new therapy used to treat drug-resistant hypertension in the clinical setting. Published human trials show substantial inter-individual variability in the blood pressure (BP) response to RDN, even when technical aspects of the treatment are standardized as much as possible between patients. Widespread acceptance of RDN for treating hypertension will require accurate identification of patients likely to respond to RDN with a fall in BP that is clinically significant in magnitude, well-maintained over time and does not cause adverse consequences. In this paper we review and evaluate clinical studies that address possible predictors of the BP response to RDN. We conclude that only one generally reliable predictor has been identified to date, namely pre-RDN BP level, although there is some evidence for a few other factors. Experimental interventions in laboratory animals provide the opportunity to explore potential predictors that are difficult to investigate in human patients. Therefore we also describe results (from our lab and others) with RDN in spontaneously hypertensive rats. Since virtually all patients receiving RDN are taking three or more antihypertensive drugs, a particular focus of our work was on how ongoing antihypertensive drug treatment might alter the BP response to RDN. We conclude that patient age (or duration of hypertension) and concomitant treatment with certain drugs can affect the blood pressure response to RDN and that this information could help predict a favorable clinical response. Copyright © 2016 Elsevier B.V. All rights reserved.

  17. Evaluation of therapy response in breast and ovarian cancer patients by positron emission tomography (PET)

    Energy Technology Data Exchange (ETDEWEB)

    Baum, R. P.; Przetak, C. [Zentralklinik Bad Berka, Clinic of Nuclear Medicine, Center for PET, Bad Berka (Germany)

    2001-09-01

    Positron emission tomography (PET) has the potential to contribute significantly to treatment planning and to the evaluation of response to therapy in patients with cancer. For disease recurrence PET imaging provides information non-invasively. The final goal is to biologically characterize an individual patients' tumor and to predict the response to treatment at the earliest possible time. Quantitative and/or semi-quantitative PET studies yield valuable information in breast cancer regarding prognosis and response to chemohormontherapy in a timely fashion. In ovarian cancer, up to now only few studies have been performed applying PET techniques for the evaluation of treatment response. These preliminary studies indicate that serial assessment of tumor metabolism by FDG-PET early during effective chemotherapy may predict subsequent response to such therapy. PET studies can be repeated without any side-effects and with low radiation exposure and results can be directly correlated with clinical laboratory data and histology. Therapy monitoring by PET could help to optimize neoadjuvant therapy protocols and to avoid ineffective preoperative therapy in non-responders, but this has to be proven in a larger number of patients and in different neoadjuvant settings such as chemotherapy, radiation therapy, hormone therapy or a combination of these.

  18. Patient predictors of response to cognitive behaviour therapy and schema therapy for depression.

    Science.gov (United States)

    Carter, Janet D; McIntosh, Virginia Vw; Jordan, Jennifer; Porter, Richard J; Douglas, Katie; Frampton, Christopher M; Joyce, Peter R

    2018-01-01

    Few studies have examined differential predictors of response to psychotherapy for depression. Greater understanding about the factors associated with therapeutic response may better enable therapists to optimise response by targeting therapy for the individual. The aim of the current exploratory study was to examine patient characteristics associated with response to cognitive behaviour therapy and schema therapy for depression. Participants were 100 outpatients in a clinical trial randomised to either cognitive behaviour therapy or schema therapy. Potential predictors of response examined included demographic, clinical, functioning, cognitive, personality and neuropsychological variables. Individuals with chronic depression and increased levels of pre-treatment negative automatic thoughts had a poorer response to both cognitive behaviour therapy and schema therapy. A treatment type interaction was found for verbal learning and memory. Lower levels of verbal learning and memory impairment markedly impacted on response to schema therapy. This was not the case for cognitive behaviour therapy, which was more impacted if verbal learning and memory was in the moderate range. Study findings are consistent with the Capitalisation Model suggesting that therapy that focuses on the person's strengths is more likely to contribute to a better outcome. Limitations were that participants were outpatients in a randomised controlled trial and may not be representative of other depressed samples. Examination of a variety of potential predictors was exploratory and requires replication.

  19. Integrative Response Therapy for Binge Eating Disorder

    Science.gov (United States)

    Robinson, Athena

    2014-01-01

    Binge Eating Disorder (BED), a chronic condition characterized by eating disorder psychopathology and physical and social disability, represents a significant public health problem. Guided Self Help (GSH) treatments for BED appear promising and may be more readily disseminable to mental health care providers, accessible to patients, and cost-effective than existing, efficacious BED specialty treatments which are limited in public health utility and impact given their time and expense demands. No existing BED GSH treatment has incorporated affect regulation models of binge eating, which appears warranted given research linking negative affect and binge eating. Integrative Response Therapy (IRT), a new group-based guided self-help treatment, based on the affect regulation model of binge eating, that has shown initial promise in a pilot sample of adults meeting DSM IV criteria for BED, is described. Fifty-four% and 67% of participants were abstinent at post-treatment and three month follow-up respectively. There was a significant reduction in the number of binge days over the previous 28 days from baseline to post-treatment [14.44 (±7.16) to 3.15 (±5.70); t=7.71, pEating Disorder Examination – Questionnaire and Emotional Eating Scale were significantly lower at post-treatment compared to baseline. 100% of IRT participants would recommend the program to a friend or family member in need. IRT’s longer-term efficacy and acceptability are presently being tested in a National Institute of Mental Health funded randomized controlled trial. PMID:24605043

  20. IL28B, HLA-C, and KIR variants additively predict response to therapy in chronic hepatitis C virus infection in a European Cohort: a cross-sectional study.

    Directory of Open Access Journals (Sweden)

    Vijayaprakash Suppiah

    2011-09-01

    Full Text Available To date, drug response genes have not proved as useful in clinical practice as was anticipated at the start of the genomic era. An exception is in the treatment of chronic hepatitis C virus (HCV genotype 1 infection with pegylated interferon-alpha and ribavirin (PegIFN/R. Viral clearance is achieved in 40%-50% of patients. Interleukin 28B (IL28B genotype predicts treatment-induced and spontaneous clearance. To improve the predictive value of this genotype, we studied the combined effect of variants of IL28B with human leukocyte antigen C (HLA-C, and its ligands the killer immunoglobulin-like receptors (KIR, which have previously been implicated in HCV viral control.We genotyped chronic hepatitis C (CHC genotype 1 patients with PegIFN/R treatment-induced clearance (n = 417 and treatment failure (n = 493, and 234 individuals with spontaneous clearance, for HLA-C C1 versus C2, presence of inhibitory and activating KIR genes, and two IL28B SNPs, rs8099917 and rs12979860. All individuals were Europeans or of European descent. IL28B SNP rs8099917 "G" was associated with absence of treatment-induced clearance (odds ratio [OR] 2.19, p = 1.27×10(-8, 1.67-2.88 and absence of spontaneous clearance (OR 3.83, p = 1.71×10(-14, 2.67-5.48 of HCV, as was rs12979860, with slightly lower ORs. The HLA-C C2C2 genotype was also over-represented in patients who failed treatment (OR 1.52, p = 0.024, 1.05-2.20, but was not associated with spontaneous clearance. Prediction of treatment failure improved from 66% with IL28B to 80% using both genes in this cohort (OR 3.78, p = 8.83×10(-6, 2.03-7.04. There was evidence that KIR2DL3 and KIR2DS2 carriage also altered HCV treatment response in combination with HLA-C and IL28B.Genotyping for IL28B, HLA-C, and KIR genes improves prediction of HCV treatment response. These findings support a role for natural killer (NK cell activation in PegIFN/R treatment-induced clearance, partially mediated by IL28B.

  1. Resting state functional connectivity predicts neurofeedback response

    Directory of Open Access Journals (Sweden)

    Dustin eScheinost

    2014-09-01

    Full Text Available Tailoring treatments to the specific needs and biology of individual patients – personalized medicine – requires delineation of reliable predictors of response. Unfortunately, these have been slow to emerge, especially in neuropsychiatric disorders. We have recently described a real-time functional magnetic resonance imaging (rt-fMRI neurofeedback protocol that can reduce contamination-related anxiety, a prominent symptom of many cases of obsessive-compulsive disorder (OCD. Individual response to this intervention is variable. Here we used patterns of brain functional connectivity, as measured by baseline resting-state fMRI (rs-fMRI, to predict improvements in contamination anxiety after neurofeedback training. Activity of a region of the orbitofrontal cortex (OFC and anterior prefrontal cortex, Brodmann area (BA 10, associated with contamination anxiety in each subject was measured in real time and presented as a neurofeedback signal, permitting subjects to learn to modulate this target brain region. We have previously reported both enhanced OFC/BA 10 control and improved anxiety in a group of subclinically anxious subjects after neurofeedback. Five individuals with contamination-related OCD who underwent the same protocol also showed improved clinical symptomatology. In both groups, these behavioral improvements were strongly correlated with baseline whole-brain connectivity in the OFC/BA 10, computed from rs-fMRI collected several days prior to neurofeedback training. These pilot data suggest that rs-fMRI can be used to identify individuals likely to benefit from rt-fMRI neurofeedback training to control contamination anxiety.

  2. Non-response to (statin) therapy

    DEFF Research Database (Denmark)

    Trompet, S; Postmus, I; Slagboom, P E

    2016-01-01

    : Baseline characteristics of non-responders to statin therapy (≤10 % LDL-C reduction) were compared with those of high responders (>40 % LDL-C reduction) through a linear regression analysis. In addition, pharmacogenetic candidate gene analysis was performed to show the effect of excluding non......-responders from the analysis. RESULTS: Non-responders to statin therapy were younger (p = 0.001), more often smoked (p ....035) compared to subjects who highly responded to pravastatin treatment. Moreover, excluding non-responders from pharmacogenetic studies yielded more robust results, as standard errors decreased. CONCLUSION: Our results suggest that non-responders to statin therapy are more likely to actually be non...

  3. Predictive Biomarkers for Bevacizumab in Anti-tumor Therapy

    Directory of Open Access Journals (Sweden)

    Qingqing PAN

    2011-07-01

    Full Text Available Bevacizumab, the monoclonal antibody of vascular endothelial growth factor (VEGF has been applied to the therapy of several neoplasms, but an appropriate biomarker to predict the efficacy has not been found. Those markers can originate from peripheral circulation, tumor tissue and genes. Some researches have found that low level of vascular cell adhesion molecule-1 (VCAM-1, E-selectin, angiopoietin 2 (Ang-2 in circulation or carbonic anhydrase 9 (CA9, CD31-microvessel density (CD31-MVD in tumor tissue can predict better activity of bevacizumab. Moreover, high level of soluble VEGFR2 (sVEGFR2 in circulation or the ratio of phosphorylated-VEGFR2 (p-VEGFR2 and VEGFR2 in tumor tissue increasing has the same predictive function. As to the gene, VEGF-634 CC, VEGF-1498 TT and VEGFR2 H472Q are only related to the side effct. Thus more clinical tirals and basic researches should be performed to find out effective biomarkers in bevacizumab’s therapy.

  4. T cell Bim levels reflect responses to anti-PD-1 cancer therapy.

    Science.gov (United States)

    Dronca, Roxana S; Liu, Xin; Harrington, Susan M; Chen, Lingling; Cao, Siyu; Kottschade, Lisa A; McWilliams, Robert R; Block, Matthew S; Nevala, Wendy K; Thompson, Michael A; Mansfield, Aaron S; Park, Sean S; Markovic, Svetomir N; Dong, Haidong

    2016-05-05

    Immune checkpoint therapy with PD-1 blockade has emerged as an effective therapy for many advanced cancers; however, only a small fraction of patients achieve durable responses. To date, there is no validated blood-based means of predicting the response to PD-1 blockade. We report that Bim is a downstream signaling molecule of the PD-1 pathway, and its detection in T cells is significantly associated with expression of PD-1 and effector T cell markers. High levels of Bim in circulating tumor-reactive (PD-1+CD11ahiCD8+) T cells were prognostic of poor survival in patients with metastatic melanoma who did not receive anti-PD-1 therapy and were also predictive of clinical benefit in patients with metastatic melanoma who were treated with anti-PD-1 therapy. Moreover, this circulating tumor-reactive T cell population significantly decreased after successful anti-PD-1 therapy. Our study supports a crucial role of Bim in both T cell activation and apoptosis as regulated by PD-1 and PD-L1 interactions in effector CD8+ T cells. Measurement of Bim levels in circulating T cells of patients with cancer may provide a less invasive strategy to predict and monitor responses to anti-PD-1 therapy, although future prospective analyses are needed to validate its utility.

  5. T cell Bim levels reflect responses to anti–PD-1 cancer therapy

    Science.gov (United States)

    Dronca, Roxana S.; Liu, Xin; Harrington, Susan M.; Chen, Lingling; Cao, Siyu; Kottschade, Lisa A.; McWilliams, Robert R.; Block, Matthew S.; Nevala, Wendy K.; Thompson, Michael A.; Mansfield, Aaron S.; Park, Sean S.; Markovic, Svetomir N.

    2016-01-01

    Immune checkpoint therapy with PD-1 blockade has emerged as an effective therapy for many advanced cancers; however, only a small fraction of patients achieve durable responses. To date, there is no validated blood-based means of predicting the response to PD-1 blockade. We report that Bim is a downstream signaling molecule of the PD-1 pathway, and its detection in T cells is significantly associated with expression of PD-1 and effector T cell markers. High levels of Bim in circulating tumor-reactive (PD-1+CD11ahiCD8+) T cells were prognostic of poor survival in patients with metastatic melanoma who did not receive anti–PD-1 therapy and were also predictive of clinical benefit in patients with metastatic melanoma who were treated with anti–PD-1 therapy. Moreover, this circulating tumor-reactive T cell population significantly decreased after successful anti–PD-1 therapy. Our study supports a crucial role of Bim in both T cell activation and apoptosis as regulated by PD-1 and PD-L1 interactions in effector CD8+ T cells. Measurement of Bim levels in circulating T cells of patients with cancer may provide a less invasive strategy to predict and monitor responses to anti–PD-1 therapy, although future prospective analyses are needed to validate its utility. PMID:27182556

  6. Personality predicts brain responses to cognitive demands.

    Science.gov (United States)

    Kumari, Veena; ffytche, Dominic H; Williams, Steven C R; Gray, Jeffrey A

    2004-11-24

    Eysenck (1981) proposed that the personality dimension of introversion- extraversion (E) reflects individual differences in a cortical arousal system modulated by reticulothalamic- cortical pathways: it is chronically more active in introverts relative to extraverts and influences cognitive performance in interaction with task parameters. A circuit with connections to this system, including the dorsolateral prefrontal cortex (DLPFC) and anterior cingulate (AC) cortex, has been identified in studies applying functional magnetic resonance imaging (fMRI) to a broad range of cognitive tasks. We examined the influence of E, assessed with the Eysenck Personality Questionnaire-Revised (Eysenck and Eysenck, 1991), in fMRI activity during an "n-back" task involving four memory loads (0-, 1-, 2-, and 3-back) and a rest condition in healthy men. To confirm the specificity of E effects, we also examined the effects of neuroticism and psychoticism (P) scores. We observed that, as predicted by Eysenck's model, the higher the E score, the greater the change in fMRI signal from rest to the 3-back condition in the DLPFC and AC. In addition, E scores were negatively associated with resting fMRI signals in the thalamus and Broca's area extending to Wernicke's area, supporting the hypothesized (negative) relationship between E and resting arousal. P scores negatively correlated with resting fMRI signal in the globus pallidus-putamen, extending previous findings of a negative relationship of schizotypy to striatal activity seen with older neuroimaging modalities to fMRI. These observations suggest that individual differences affect brain responses during cognitive activity and at rest and provide evidence for the hypothesized neurobiological basis of personality.

  7. Modeling and predicting tissue movement and deformation for high intensity focused ultrasound therapy.

    Directory of Open Access Journals (Sweden)

    Xiangyun Liao

    Full Text Available In ultrasound-guided High Intensity Focused Ultrasound (HIFU therapy, the target tissue (such as a tumor often moves and/or deforms in response to an external force. This problem creates difficulties in treating patients and can lead to the destruction of normal tissue. In order to solve this problem, we present a novel method to model and predict the movement and deformation of the target tissue during ultrasound-guided HIFU therapy.Our method computationally predicts the position of the target tissue under external force. This prediction allows appropriate adjustments in the focal region during the application of HIFU so that the treatment head is kept aligned with the diseased tissue through the course of therapy. To accomplish this goal, we utilize the cow tissue as the experimental target tissue to collect spatial sequences of ultrasound images using the HIFU equipment. A Geodesic Localized Chan-Vese (GLCV model is developed to segment the target tissue images. A 3D target tissue model is built based on the segmented results. A versatile particle framework is constructed based on Smoothed Particle Hydrodynamics (SPH to model the movement and deformation of the target tissue. Further, an iterative parameter estimation algorithm is utilized to determine the essential parameters of the versatile particle framework. Finally, the versatile particle framework with the determined parameters is used to estimate the movement and deformation of the target tissue.To validate our method, we compare the predicted contours with the ground truth contours. We found that the lowest, highest and average Dice Similarity Coefficient (DSC values between predicted and ground truth contours were, respectively, 0.9615, 0.9770 and 0.9697.Our experimental result indicates that the proposed method can effectively predict the dynamic contours of the moving and deforming tissue during ultrasound-guided HIFU therapy.

  8. Open source machine-learning algorithms for the prediction of optimal cancer drug therapies.

    Science.gov (United States)

    Huang, Cai; Mezencev, Roman; McDonald, John F; Vannberg, Fredrik

    2017-01-01

    Precision medicine is a rapidly growing area of modern medical science and open source machine-learning codes promise to be a critical component for the successful development of standardized and automated analysis of patient data. One important goal of precision cancer medicine is the accurate prediction of optimal drug therapies from the genomic profiles of individual patient tumors. We introduce here an open source software platform that employs a highly versatile support vector machine (SVM) algorithm combined with a standard recursive feature elimination (RFE) approach to predict personalized drug responses from gene expression profiles. Drug specific models were built using gene expression and drug response data from the National Cancer Institute panel of 60 human cancer cell lines (NCI-60). The models are highly accurate in predicting the drug responsiveness of a variety of cancer cell lines including those comprising the recent NCI-DREAM Challenge. We demonstrate that predictive accuracy is optimized when the learning dataset utilizes all probe-set expression values from a diversity of cancer cell types without pre-filtering for genes generally considered to be "drivers" of cancer onset/progression. Application of our models to publically available ovarian cancer (OC) patient gene expression datasets generated predictions consistent with observed responses previously reported in the literature. By making our algorithm "open source", we hope to facilitate its testing in a variety of cancer types and contexts leading to community-driven improvements and refinements in subsequent applications.

  9. Quality of Life in Relation to Pain Response to Radiation Therapy for Painful Bone Metastases

    NARCIS (Netherlands)

    Westhoff, Paulien G.; De Graeff, Alexander|info:eu-repo/dai/nl/187695997; Monninkhof, Evelyn M.|info:eu-repo/dai/nl/260610178; Pomp, Jacqueline; Van Vulpen, Marco|info:eu-repo/dai/nl/250581035; Leer, Jan Willem H; Marijnen, Corrie A M; Van Der Linden, Yvette M.

    2015-01-01

    Purpose: To study quality of life (QoL) in responders and nonresponders after radiation therapy for painful bone metastases; and to identify factors predictive for a pain response. Patients and Methods: The prospectively collected data of 956 patients with breast, prostate, and lung cancer within

  10. Quality of Life in Relation to Pain Response to Radiation Therapy for Painful Bone Metastases

    NARCIS (Netherlands)

    Westhoff, P.G.; Graeff, A. de; Monninkhof, E.M.; Pomp, J.; Vulpen, M. van; Leer, J.W.; Marijnen, C.A.; Linden, Y.M. van der

    2015-01-01

    PURPOSE: To study quality of life (QoL) in responders and nonresponders after radiation therapy for painful bone metastases; and to identify factors predictive for a pain response. PATIENTS AND METHODS: The prospectively collected data of 956 patients with breast, prostate, and lung cancer within

  11. Risk factors of incomplete response to proton pump inhibitor therapy in patients with mild erosive esophagitis

    Directory of Open Access Journals (Sweden)

    Sung-Shuo Kao

    2015-03-01

    Conclusion: Of the patients with Los Angeles Grade A/B erosive esophagitis, 21.6% failed to have complete symptom resolution following 8-week PPI therapy. Globus and insomnia are two independent factors predicting incomplete symptom response in patients with mild erosive esophagitis.

  12. Atypical and Typical Winter Depressive Symptoms and Responsiveness to Light Therapy, Cognitive-Behavioral Therapy, or Combination Treatment

    Science.gov (United States)

    2005-01-01

    Cognitive - Behavioral Therapy , or Combination Treatment” Name of Candidate: Leigh G. Johnson Master of Science Degree 2005 Thesis and Abstract...and Typical Winter Depressive Symptoms and Responsiveness to Light Therapy , Cognitive - Behavioral Therapy , or Combination Treatment 5a. CONTRACT NUMBER...entitled: “Atypical and Typical Winter Depressive Symptoms and Responsiveness to Light Therapy , Cognitive - Behavioral Therapy , or

  13. Response predictions using the observed autocorrelation function

    DEFF Research Database (Denmark)

    Nielsen, Ulrik Dam; H. Brodtkorb, Astrid; Jensen, Jørgen Juncher

    2017-01-01

    operations (crane lifts, helicopter landings, etc.), as a specic prediction can be used to inform whether it is safe, or not, to carry out the particular operation within the nearest time horizon. The examined prediction procedure relies on observations of the correlation structure of the wave...

  14. Applying Quantitative CT Image Feature Analysis to Predict Response of Ovarian Cancer Patients to Chemotherapy.

    Science.gov (United States)

    Danala, Gopichandh; Thai, Theresa; Gunderson, Camille C; Moxley, Katherine M; Moore, Kathleen; Mannel, Robert S; Liu, Hong; Zheng, Bin; Qiu, Yuchen

    2017-10-01

    The study aimed to investigate the role of applying quantitative image features computed from computed tomography (CT) images for early prediction of tumor response to chemotherapy in the clinical trials for treating ovarian cancer patients. A dataset involving 91 patients was retrospectively assembled. Each patient had two sets of pre- and post-therapy CT images. A computer-aided detection scheme was applied to segment metastatic tumors previously tracked by radiologists on CT images and computed image features. Two initial feature pools were built using image features computed from pre-therapy CT images only and image feature difference computed from both pre- and post-therapy images. A feature selection method was applied to select optimal features, and an equal-weighted fusion method was used to generate a new quantitative imaging marker from each pool to predict 6-month progression-free survival. The prediction accuracy between quantitative imaging markers and the Response Evaluation Criteria in Solid Tumors (RECIST) criteria was also compared. The highest areas under the receiver operating characteristic curve are 0.684 ± 0.056 and 0.771 ± 0.050 when using a single image feature computed from pre-therapy CT images and feature difference computed from pre- and post-therapy CT images, respectively. Using two corresponding fusion-based image markers, the areas under the receiver operating characteristic curve significantly increased to 0.810 ± 0.045 and 0.829 ± 0.043 (P imaging markers and RECIST, respectively. This study demonstrated the feasibility of predicting patients' response to chemotherapy using quantitative imaging markers computed from pre-therapy CT images. However, using image feature difference computed between pre- and post-therapy CT images yielded higher prediction accuracy. Copyright © 2017 The Association of University Radiologists. Published by Elsevier Inc. All rights reserved.

  15. Inadequate Response to Therapy as a Predictor of Suicide.

    Science.gov (United States)

    Dahlsgaard, Katherine K.; Beck, Aaron T.; Brown, Gregory K.

    1998-01-01

    The role of response to cognitive therapy as a predictor of suicide was investigated by comparing 17 outpatients with mood disorders who committed suicide with 17 matched patients who did not commit suicide. Significant differences were found on several variables including higher levels of hopelessness at termination of therapy. (Author/EMK)

  16. Multimodal OCT for complex assessment of tumors response to therapy

    Science.gov (United States)

    Sirotkina, Marina A.; Kiseleva, Elena B.; Gubarkova, Ekaterina V.; Matveev, Lev A.; Zaitsev, Vladimir Yu.; Matveyev, Alexander L.; Shirmanova, Marina V.; Sovetsky, Alexander A.; Moiseev, Alexander A.; Zagaynova, Elena V.; Vitkin, Alex; Gladkova, Natalia D.

    2017-07-01

    Multimodal OCT is a promising tool for monitoring of individual tumor response to antitumor therapies. The changes of tumor cells, connective tissue, microcirculation and stiffness can be estimated simultaneously in real time with high resolution.

  17. An observation on the variance of a predicted response in ...

    African Journals Online (AJOL)

    In studying individual parameters and the predicted response in regression analysis, three important properties are usually distinguished. These are bias, variance and mean-square error. The choice of a predicted response has to be made on a balance of these properties and computational simplicity. To avoid over fitting, ...

  18. Therapygenetics: Using genetic markers to predict response to psychological treatment for mood and anxiety disorders

    OpenAIRE

    Lester, Kathryn J; Eley, Thalia C

    2013-01-01

    Abstract Considerable variation is evident in response to psychological therapies for mood and anxiety disorders. Genetic factors alongside environmental variables and gene-environment interactions are implicated in the etiology of these disorders and it is plausible that these same factors may also be important in predicting individual differences in response to psychological treatment. In this article, we review the evidence that genetic variation influences psychological treatment outcomes...

  19. Individualized therapies in colorectal cancer: KRAS as a marker for response to EGFR-targeted therapy

    Directory of Open Access Journals (Sweden)

    Li Kuiyuan

    2009-04-01

    Full Text Available Abstract Individualized therapies that are tailored to a patient's genetic composition will be of tremendous value for treatment of cancer. Recently, Kirsten ras (KRAS status has emerged as a predictor of response to epidermal growth factor receptor (EGFR targeted therapies. In this article, we will discuss targeted therapies for colorectal cancers (CRC based on EGFR signaling pathway and review published data about the potential usefulness of KRAS as a biological marker for response to these therapies. Results from relevant studies published since 2005 and unpublished results presented at national meetings were retrieved and summarized. These studies reflected response (or lack of response to EGFR-targeted therapies in patients with metastatic CRC as a function of KRAS status. It has become clear that patients with colorectal cancer whose tumor has an activating mutation in KRAS do not respond to monoclonal antibody therapies targeting EGFR. It should now become a standard practice that any patients being considered for EGFR targeted therapies have their tumors tested for KRAS status and only those with wild-type KRAS being offered such therapies.

  20. Clinical Prediction Rules for Physical Therapy Interventions: A Systematic Review

    Science.gov (United States)

    Beneciuk, Jason M; Bishop, Mark D; George, Steven Z

    2009-01-01

    Background and Purpose: Clinical prediction rules (CPRs) involving physical therapy interventions have been published recently. The quality of the studies used to develop the CPRs was not previously considered, a fact that has potential implications for clinical applications and future research. The purpose of this systematic review was to determine the quality of published CPRs developed for physical therapy interventions. Methods: Relevant databases were searched up to June 2008. Studies were included in this review if the explicit purpose was to develop a CPR for conditions commonly treated by physical therapists. Validated CPRs were excluded from this review. Study quality was independently determined by 3 reviewers using standard 18-item criteria for assessing the methodological quality of prognostic studies. Percentage of agreement was calculated for each criterion, and the intraclass correlation coefficient (ICC) was determined for overall quality scores. Results: Ten studies met the inclusion criteria and were included in this review. Percentage of agreement for individual criteria ranged from 90% to 100%, and the ICC for the overall quality score was .73 (95% confidence interval=.27–.92). Criteria commonly not met were adequate description of inclusion or exclusion criteria, inclusion of an inception cohort, adequate follow-up, masked assessments, sufficient sample sizes, and assessments of potential psychosocial factors. Quality scores for individual studies ranged from 48.2% to 74.0%. Discussion and Conclusion: Validation studies are rarely reported in the literature; therefore, CPRs derived from high-quality studies may have the best potential for use in clinical settings. Investigators planning future studies of physical therapy CPRs should consider including inception cohorts, using longer follow-up times, performing masked assessments, recruiting larger sample sizes, and incorporating psychological and psychosocial assessments. PMID:19095806

  1. Extreme wave and wind response predictions

    DEFF Research Database (Denmark)

    Jensen, Jørgen Juncher; Olsen, Anders S.; Mansour, Alaa E.

    2011-01-01

    The aim of the paper is to advocate effective stochastic procedures, based on the First Order Reliability Method (FORM) and Monte Carlo simulations (MCS), for extreme value predictions related to wave and wind-induced loads.Due to the efficient optimization procedures implemented in standard FORM...

  2. Prediction of psilocybin response in healthy volunteers

    National Research Council Canada - National Science Library

    Studerus, Erich; Gamma, Alex; Kometer, Michael; Vollenweider, Franz X

    2012-01-01

    Responses to hallucinogenic drugs, such as psilocybin, are believed to be critically dependent on the user's personality, current mood state, drug pre-experiences, expectancies, and social and environmental variables...

  3. Slot Machine Response Frequency Predicts Pathological Gambling

    DEFF Research Database (Denmark)

    Linnet, Jakob; Rømer Thomsen, Kristine; Møller, Arne

    2013-01-01

    Slot machines are among the most addictive forms of gambling, and pathological gambling slot machine players represent the largest group of treatment seekers, accounting for 35% to 93% of the population. Pathological gambling sufferers have significantly higher response frequency (games / time......) on slot machines compared with non-problem gamblers, which may suggest increased reinforcement of the gambling behavior in pathological gambling. However, to date it is unknown whether or not the increased response frequency in pathological gambling is associated with symptom severity of the disorder....... This study tested the hypothesis that response frequency is associated with symptom severity in pathological gambling. We tested response frequency among twenty-two pathological gambling sufferers and twenty-one non-problem gamblers on a commercially available slot machine, and screened for pathological...

  4. IP-10 predicts the first phase decline of HCV RNA and overall viral response to therapy in patients co-infected with chronic hepatitis C virus infection and HIV

    DEFF Research Database (Denmark)

    Falconer, Karolin; Askarieh, Galia; Weis, Nina Margrethe

    2010-01-01

    The aim of this study was to investigate the utility of baseline plasma interferon-gamma inducible protein-10 (IP-10) levels in human immunodeficiency virus (HIV)-hepatitis C virus (HCV) co-infected patients. Baseline IP-10 was monitored during HCV combination therapy in 21 HIV-HCV co......-10 HIV-HCV co-infected patients, and may thus be useful in encouraging such difficult-to-treat patients to initiate therapy....

  5. Response to targeted therapy in urachal adenocarcinoma

    Directory of Open Access Journals (Sweden)

    Isabella Testa

    2014-12-01

    Full Text Available We report the case of a young woman diagnosed with metastatic urachal carcinoma. A multimodal approach was used for the management of this patient. Due to disease progression despite surgery and two different chemotherapy regimens (neoadjuvant capecitabine + irinotecan + oxaliplatin and docetaxel + cisplatin after surgery, treatment with sunitinib was eventually started. Treatment with sunitinib resulted in stable disease and improvement of symptoms. Sunitinib was discontinued due to the occurrence of metrorrhagia, and restarted one week later. Disease eventually progressed and the patient died 18 months after the onset of symptoms. This is the first report on the use of sunitinib for the management of urachal carcinoma and provides initial evidence supporting the use of targeted therapy in this setting.

  6. Neopterin as a Marker of Response to Antiviral Therapy in Hepatitis C Virus Patients

    Directory of Open Access Journals (Sweden)

    Gregory F. Oxenkrug

    2012-01-01

    Full Text Available Predicting the efficacy of antiviral treatment of hepatitis C virus (HCV is of importance for both patient well-being and health care expense. The expression of interferon-stimulated genes (IFN-SGs in the liver was suggested as a marker of response to anti-viral therapy. IFN-SGs encode the guanosine triphosphate cyclohydrolase 1 (GTPCH, a rate-limiting enzyme of pteridines biosynthesis. Neopterin, a stable byproduct of GTPCH-catalyzed reaction, is used as a marker of interferon-induced GTPCH activation. We hypothesized that assessment of neopterin concentrations might predict the response to antiviral therapy. Neopterin concentrations were evaluated in 260 HCV patients treated by pegylated interferon combined with ribavirin. Mean and median pretreatment neopterin concentrations were lower in patients with sustained virological response than in nonresponders. The rate of response was twofold higher among patients with pretreatment neopterin levels <16 nmol/L than in patients with neopterin levels ≥16 nmol/L, even after controlling for HCV genotype status. Our study suggests that the pretreatment level of neopterin might be used in routine clinical practice as rapid and cost-effective marker to predict the response to antiviral therapy in HCV patients.

  7. What predicts outcome, response, and drop-out in CBT of depressive adults? a naturalistic study.

    Science.gov (United States)

    Schindler, Amrei; Hiller, Wolfgang; Witthöft, Michael

    2013-05-01

    The efficacy of CBT for unipolar depressive disorders is well established, yet not all patients improve or tolerate treatment. To identify factors associated with symptomatic outcome, response, and drop-out in depressive patients under naturalistic CBT. 193 patients with major depression or dysthymia were tested. Sociodemographic and clinical variables were entered as predictors in hierarchical regression analyses. A higher degree of pretreatment depression, early improvement, and completion of therapy were identified as predictors for symptomatic change and response. Drop-out was predicted by concurrent personality disorder, less positive outcome expectancies, and by failure to improve early in treatment. Our results highlight the importance of early response to predict improvement in routine CBT. Attempts to refine the quality of treatment programs should focus on avoiding premature termination (drop-out) and consider motivational factors in more depth. Routinely administered standardized assessments would enhance symptom monitoring and help to identify persons at risk of not improving under therapy.

  8. Predicting dropout in outpatient dialectical behavior therapy with patients with borderline personality disorder receiving psychiatric disability.

    Science.gov (United States)

    Landes, Sara J; Chalker, Samantha A; Comtois, Katherine Anne

    2016-01-01

    Rates of treatment dropout in outpatient Dialectical Behavior Therapy (DBT) in the community can be as high as 24 % to 58 %, making dropout a great concern. The primary purpose of this article was to examine predictors of dropout from DBT in a community mental health setting. Participants were 56 consumers with borderline personality disorder (BPD) who were psychiatrically disabled participating in a larger feasibility trial of Dialectical Behavior Therapy- Accepting the Challenges of Exiting the System. The following variables were examined to see whether they predicted dropout in DBT: age, education level, baseline level of distress, baseline level of non-acceptance of emotional responses, and skills module in which a consumer started DBT skills group. These variables were chosen based on known predictors of dropout in consumers with BPD and in DBT, as well as an interest in what naturally occurring variables might impact dropout. The dropout rate in this sample was 51.8 %. Results of the logistic regression show that younger age, higher levels of baseline distress, and a higher level of baseline non-acceptance of emotional responses were significantly associated with dropout. The DBT skills module in which an individual started group did not predict dropout. The implications of these findings are that knowledge of consumer age and pretreatment levels of distress and non-acceptance of emotional responses can impact providers' choice of commitment and treatment strategies to reduce dropout. Future research should examine these strategies, as well as the impact of predictor variables on outcome and reasons for dropout.

  9. IP-10 predicts the first phase decline of HCV RNA and overall viral response to therapy in patients co-infected with chronic hepatitis C virus infection and HIV

    DEFF Research Database (Denmark)

    Falconer, Karolin; Askarieh, Galia; Weis, Nina Margrethe

    2010-01-01

    The aim of this study was to investigate the utility of baseline plasma interferon-gamma inducible protein-10 (IP-10) levels in human immunodeficiency virus (HIV)-hepatitis C virus (HCV) co-infected patients. Baseline IP-10 was monitored during HCV combination therapy in 21 HIV-HCV co-infected pa......The aim of this study was to investigate the utility of baseline plasma interferon-gamma inducible protein-10 (IP-10) levels in human immunodeficiency virus (HIV)-hepatitis C virus (HCV) co-infected patients. Baseline IP-10 was monitored during HCV combination therapy in 21 HIV-HCV co......-infected patients (HCV genotype 1 (n = 16), 2 (n = 2), and 3 (n = 3)). Lower baseline IP-10 was significantly associated with a rapid decline in HCV RNA, in particular with the first phase reduction, and similar cut-off levels ( 600 pg/ml) as in HCV mono-infected patients apply. In conclusion, baseline IP......-10 therapy in HIV-HCV co-infected patients, and may thus be useful in encouraging such difficult-to-treat patients to initiate therapy....

  10. Field Response Prediction: Framing the problem.

    Energy Technology Data Exchange (ETDEWEB)

    Cabrera-Palmer, Belkis [Sandia National Lab. (SNL-NM), Albuquerque, NM (United States)

    2017-06-01

    Predicting the performance of radiation detection systems at field sites based on measured performance acquired under controlled conditions at test locations, e.g., the Nevada National Security Site (NNSS), remains an unsolved and standing issue within DNDO’s testing methodology. Detector performance can be defined in terms of the system’s ability to detect and/or identify a given source or set of sources, and depends on the signal generated by the detector for the given measurement configuration (i.e., source strength, distance, time, surrounding materials, etc.) and on the quality of the detection algorithm. Detector performance is usually evaluated in the performance and operational testing phases, where the measurement configurations are selected to represent radiation source and background configurations of interest to security applications.

  11. Molecular stratification of metastatic melanoma using gene expression profiling: Prediction of survival outcome and benefit from molecular targeted therapy.

    Science.gov (United States)

    Cirenajwis, Helena; Ekedahl, Henrik; Lauss, Martin; Harbst, Katja; Carneiro, Ana; Enoksson, Jens; Rosengren, Frida; Werner-Hartman, Linda; Törngren, Therese; Kvist, Anders; Fredlund, Erik; Bendahl, Pär-Ola; Jirström, Karin; Lundgren, Lotta; Howlin, Jillian; Borg, Åke; Gruvberger-Saal, Sofia K; Saal, Lao H; Nielsen, Kari; Ringnér, Markus; Tsao, Hensin; Olsson, Håkan; Ingvar, Christian; Staaf, Johan; Jönsson, Göran

    2015-05-20

    Melanoma is currently divided on a genetic level according to mutational status. However, this classification does not optimally predict prognosis. In prior studies, we have defined gene expression phenotypes (high-immune, pigmentation, proliferative and normal-like), which are predictive of survival outcome as well as informative of biology. Herein, we employed a population-based metastatic melanoma cohort and external cohorts to determine the prognostic and predictive significance of the gene expression phenotypes. We performed expression profiling on 214 cutaneous melanoma tumors and found an increased risk of developing distant metastases in the pigmentation (HR, 1.9; 95% CI, 1.05-3.28; P=0.03) and proliferative (HR, 2.8; 95% CI, 1.43-5.57; P=0.003) groups as compared to the high-immune response group. Further genetic characterization of melanomas using targeted deep-sequencing revealed similar mutational patterns across these phenotypes. We also used publicly available expression profiling data from melanoma patients treated with targeted or vaccine therapy in order to determine if our signatures predicted therapeutic response. In patients receiving targeted therapy, melanomas resistant to targeted therapy were enriched in the MITF-low proliferative subtype as compared to pre-treatment biopsies (P=0.02). In summary, the melanoma gene expression phenotypes are highly predictive of survival outcome and can further help to discriminate patients responding to targeted therapy.

  12. Predicting Improvement in Writer's Cramp Symptoms following Botulinum Neurotoxin Injection Therapy

    Directory of Open Access Journals (Sweden)

    Mallory Jackman

    2016-09-01

    Full Text Available Introduction: Writer's cramp is a specific focal hand dystonia causing abnormal posturing and tremor in the upper limb. The most popular medical intervention, botulinum neurotoxin type A (BoNT-A therapy, is variably effective for 50–70% of patients. BoNT-A non-responders undergo ineffective treatment and may experience significant side effects. Various assessments have been used to determine response prediction to BoNT-A, but not in the same population of patients. Methods: A comprehensive assessment was employed to measure various symptom aspects. Clinical scales, full upper-limb kinematic measures, self-report, and task performance measures were assessed for nine writer's cramp patients at baseline. Patients received two BoNT-A injections then were classified as responders or non-responders based on a quantified self-report measure. Baseline scores were compared between groups, across all measures, to determine which scores predicted a positive BoNT-A response. Results: Five of nine patients were responders. No kinematic measures were predictably different between groups. Analyses revealed three features that predicted a favorable response and separated the two groups: higher than average cramp severity and cramp frequency, and below average cramp latency. Discussion: Non-kinematic measures appear to be superior in making such predictions. Specifically, measures of cramp severity, frequency, and latency during performance of a specific set of writing and drawing tasks were predictive factors. Since kinematic was not used to determine the injection pattern and the injections were visually guided, it may still be possible to use individual patient kinematics for better outcomes. 

  13. Radiation response prediction of single mode fibers

    Science.gov (United States)

    Friebele, E. J.; Askins, Charles G.; Brambani, Louise A.; Dorsey, Kenneth L.; Griscom, David L.; Gingerich, Michael E.; Harrington, Calvin C.; Shaw, Cathy M.; Tsai, Tsung-Ein; Paek, Un-Chul

    1988-03-01

    Fiber optic transmission systems, because of their extraordinary channel capacity and decreasing cost, are rapidly becoming the preferred terrestrial transmission media of the nation's long distance, inter-city telecommunications infrastructure. Since the commercial telephone network forms the foundation for emergency communication in the event of a national crisis or emergency, additional requirements are placed on the fibers and components being installed. One of the most stressing environments for the fiber consists of fallout subsequent to a nuclear attack. The susceptibility of some of types of commercially available fiber optic cable to optical darkening (and hence increased signal loss) from exposure to ionizing radiation raises serious questions about the survivability of such systems in the reconstitution phase of a nuclear conflict. There is a large body of knowledge available on the effects of gamma radiation on the older multimode fiber cables. However, there are critically important knowledge gaps with respect to the newer single mode cables which are employed in the inter-city fiber transmission links being installed today. This document is a final report of a two year program funded by NCS at NRL, which was the first systematic study of the interrelationship of fiber fabrication parameters and radiation-induced loss. A rudimentary regression model was developed for predicting the loss induced by a fallout exposure at -35 C.

  14. Deterministic Predictions of Vessel Responses Based on Past Measurements

    DEFF Research Database (Denmark)

    Nielsen, Ulrik Dam; Jensen, Jørgen Juncher

    2017-01-01

    The paper deals with a prediction procedure from which global wave-induced responses can be deterministically predicted a short time, 10-50 s, ahead of current time. The procedure relies on the autocorrelation function and takes into account prior measurements only; i.e. knowledge about wave cond...

  15. Model Predictive Control based on Finite Impulse Response Models

    DEFF Research Database (Denmark)

    Prasath, Guru; Jørgensen, John Bagterp

    2008-01-01

    We develop a regularized l2 finite impulse response (FIR) predictive controller with input and input-rate constraints. Feedback is based on a simple constant output disturbance filter. The performance of the predictive controller in the face of plant-model mismatch is investigated by simulations...

  16. Extended RAS Gene Mutation Testing in Metastatic Colorectal Carcinoma to Predict Response to Anti-Epidermal Growth Factor Receptor Monoclonal Antibody Therapy: American Society of Clinical Oncology Provisional Clinical Opinion Update 2015.

    Science.gov (United States)

    Allegra, Carmen J; Rumble, R Bryan; Hamilton, Stanley R; Mangu, Pamela B; Roach, Nancy; Hantel, Alexander; Schilsky, Richard L

    2016-01-10

    An American Society of Clinical Oncology Provisional Clinical Opinion (PCO) offers timely clinical direction after publication or presentation of potentially practice-changing data from major studies. This PCO update addresses the utility of extended RAS gene mutation testing in patients with metastatic colorectal cancer (mCRC) to detect resistance to anti-epidermal growth factor receptor (EGFR) monoclonal antibody (MoAb) therapy. Recent results from phase II and III clinical trials in mCRC demonstrate that patients whose tumors harbor RAS mutations in exons 2 (codons 12 and 13), 3 (codons 59 and 61), and 4 (codons 117 and 146) are unlikely to benefit from therapy with MoAbs directed against EGFR, when used as monotherapy or combined with chemotherapy. In addition to the evidence reviewed in the original PCO, 11 systematic reviews with meta-analyses, two retrospective analyses, and two health technology assessments based on a systematic review were obtained. These evaluated the outcomes for patients with mCRC with no mutation detected or presence of mutation in additional exons in KRAS and NRAS. PCO: All patients with mCRC who are candidates for anti-EGFR antibody therapy should have their tumor tested in a Clinical Laboratory Improvement Amendments-certified laboratory for mutations in both KRAS and NRAS exons 2 (codons 12 and 13), 3 (codons 59 and 61), and 4 (codons 117 and 146). The weight of current evidence indicates that anti-EGFR MoAb therapy should only be considered for treatment of patients whose tumor is determined to not have mutations detected after such extended RAS testing. © 2015 by American Society of Clinical Oncology.

  17. Predictive analysis of photodynamic therapy applied to esophagus cancer

    Science.gov (United States)

    Fanjul-Vélez, F.; del Campo-Gutiérrez, M.; Ortega-Quijano, N.; Arce-Diego, J. L.

    2008-04-01

    The use of optical techniques in medicine has revolutionized in many cases the medical praxis, providing new tools for practitioners or improving the existing ones in the fight against diseases. The application of this technology comprises mainly two branches, characterization and treatment of biological tissues. Photodynamic Therapy (PDT) provides a solution for malignant tissue destruction, by means of the inoculation of a photosensitizer and irradiation by an optical source. The key factor of the procedure is the localization of the damage to avoid collateral harmful effects. The volume of tissue destroyed depends on the type of photosensitizer inoculated, both on its reactive characteristics and its distribution inside the tissue, and also on the specific properties of the optical source, that is, the optical power, wavelength and exposition time. In this work, a model for PDT based on the one-dimensional diffusion equation, extensible to 3D, to estimate the optical distribution in tissue, and on photosensitizer parameters to take into account the photobleaching effect is proposed. The application to esophagus cancer allows the selection of the right optical source parameters, like irradiance, wavelength or exposition time, in order to predict the area of tissue destruction.

  18. Predictive parameters of response to desmopressin in primary nocturnal enuresis.

    Science.gov (United States)

    Van Herzeele, Charlotte; Evans, Jonathan; Eggert, Paul; Lottmann, Henri; Norgaard, Jens Peter; Vande Walle, Johan

    2015-08-01

    prospective study is ethically hardly defendable for children if data are available from previous literature [1]; therefore, a re-analysis was the appropriate choice. The study confirms the predictive value of age, number of wet nights a week and nocturnal diuresis [1,2]. The study demonstrates that desmopressin response rates are higher in children with greater age, limited number of wet nights a week and nocturnal polyuria. Only a minority of a primary nocturnal enuresis population, based on history alone, had nocturnal polyuria. The majority had a low maximum voided volume. The results clearly stress the importance of a frequency/volume chart for individualizing therapy to the characteristics, thereby resulting in elevated success rates. Registration number of clinical trial: Clinical Trials.gov NCT00245479. Copyright © 2015 Journal of Pediatric Urology Company. Published by Elsevier Ltd. All rights reserved.

  19. Biofeedback therapy for pediatric headache: factors associated with response.

    Science.gov (United States)

    Blume, Heidi K; Brockman, Libby N; Breuner, Cora C

    2012-10-01

    The goal of this study was to measure the effect of biofeedback therapy on pediatric headache and to identify factors associated with response to biofeedback therapy. In the United States, 17% of children have frequent or severe headaches. Biofeedback therapy (BFT) appears to be an effective treatment for headaches in adults and is often recommended for children with headaches, but there are few data in the pediatric population. It is also not clear which patients are most likely to benefit from biofeedback therapy. We examined the records of patients, aged 8 to 18 years old, who were referred to a pediatric BFT clinic for management of headache between 2004 and 2008. We extracted data regarding patient and headache characteristics, medication use, family history, and measures of depression, anxiety, and somatization. Chronic headache was defined as ≥4 headache days/week. Positive response to biofeedback was defined as a 50% reduction in number of headache days/week or hours/week, or ≥3-point decrease in severity (0-10 scale) between first and last visits. We analyzed the responder rate for those with episodic and chronic headaches and performed multivariable analysis to determine what factors were associated with headache response to biofeedback therapy. We analyzed records from 132 children who attended ≥2 biofeedback sessions. Median headache frequency dropped from 3.5 to 2 headache days/week between the first and last visits. The response rate was 58% overall; 48% for chronic headaches and 73% episodic headaches. In multivariate analysis, ability to raise hand temperature by >3°F at the last visit and use of selective serotonin reuptake inhibitors (SSRIs) were associated with a positive response, and preventive medication use was associated with nonresponse. Anxiety, depression, and somatization were not significantly associated with response to biofeedback therapy. Biofeedback therapy appears to be an effective treatment for children and adolescents

  20. Atypical and Typical Winter Depressive Symptoms and Responsiveness to Light Therapy, Cognitive-Behavioral Therapy, or Combination Treatment

    National Research Council Canada - National Science Library

    Johnson, Leigh G; Rohan, Kelly J

    2005-01-01

    ...) differentially predict treatment outcome. Participants (N=61) fulfilled criteria for Major Depression, Recurrent with Seasonal Pattern, and completed a 6-week randomized clinical trial comparing light therapy (LT...

  1. Response to combination antiretroviral therapy: variation by age

    DEFF Research Database (Denmark)

    Lundgren, Jens

    2008-01-01

    OBJECTIVE: To provide information on responses to combination antiretroviral therapy in children, adolescents and older HIV-infected persons. DESIGN AND SETTING: Multicohort collaboration of 33 European cohorts. SUBJECTS:: Forty-nine thousand nine hundred and twenty-one antiretroviral-naive indiv...... CD4 cell counts, may place this group at increased clinical risk. The poorer virological responses in children may increase the likelihood of emergence of resistance....

  2. CD4 + CELL RESPONSE TO ANTI-RETROVIRAL THERAPY (ARTs ...

    African Journals Online (AJOL)

    East African Medical Journal Vol. 90 No. 12 (Supplement) December 2013. CD4 + CELL RESPONSE TO ANTI-RETROVIRAL THERAPY (ARTs) IN ROUTINE CLINICAL CARE OVER ONE YEAR. PERIOD IN A COHORT OF HAART NAIVE, HIV POSITIVE KENYAN PATIENTS. C. F. Otieno, MBChB, MMed (Int. Med), ...

  3. Cortisol response to critical illness: Effect of intensive insulin therapy

    NARCIS (Netherlands)

    I. Vanhorebeek (Ilse); R.P. Peeters (Robin); S.V. Perre (Sarah Vander); I. Jans (Ivo); P.J. Wouters (Pieter); K. Skogstrand (Kristin); T.K. Hansen (Troels); R. Bouillon (Roger); G. van den Berghe (Greet)

    2006-01-01

    textabstractContext: Both excessive and insufficient activation of the hypothalamic-pituitary-adrenal axis in response to critical illness is associated with increased mortality. Objective: The objective of the study was to study the effect of intensive insulin therapy, recently shown to reduce

  4. Systemic inflammation response index (SIRI) predicts prognosis in hepatocellular carcinoma patients

    Science.gov (United States)

    Xu, Litao; Yu, Shulin; Zhuang, Liping; Wang, Peng; Shen, Yehua; Lin, Junhua; Meng, Zhiqiang

    2017-01-01

    The systemic inflammation response index (SIRI) is a useful tool for predicting prognosis in some types of cancer. In this retrospective study, we evaluated the efficacy of SIRI in predicting overall survival in hepatocellular carcinoma (HCC) patients following local or systemic therapy. A cutoff value of 1.05 was identified for SIRI using ROC analysis in a training patient cohort. In the validation cohort, survival analysis revealed that median overall survival was longer in HCC patients with SIRI scores SIRI was associated with overall survival and was more predictive of overall survival that the AFP level or Child-Pugh score. However, SIRI and Barcelona Clinic Liver Cancer (BCLC) stage were equally effective for predicting survival. In addition, HCC patients with BCLC stage C had higher SIRI scores and poorer overall survival. SIRI also correlated with liver function parameters. Thus SIRI may be a convenient, low cost and reliable tumor marker for predicting prognosis in HCC patients. PMID:28430597

  5. Predicting the response to CTLA-4 blockade by longitudinal noninvasive monitoring of CD8 T cells.

    Science.gov (United States)

    Rashidian, Mohammad; Ingram, Jessica R; Dougan, Michael; Dongre, Anushka; Whang, Katherine A; LeGall, Camille; Cragnolini, Juan J; Bierie, Brian; Gostissa, Monica; Gorman, James; Grotenbreg, Gijsbert M; Bhan, Atul; Weinberg, Robert A; Ploegh, Hidde L

    2017-08-07

    Immunotherapy using checkpoint-blocking antibodies against targets such as CTLA-4 and PD-1 can cure melanoma and non-small cell lung cancer in a subset of patients. The presence of CD8 T cells in the tumor correlates with improved survival. We show that immuno-positron emission tomography (immuno-PET) can visualize tumors by detecting infiltrating lymphocytes and, through longitudinal observation of individual animals, distinguish responding tumors from those that do not respond to therapy. We used 89Zr-labeled PEGylated single-domain antibody fragments (VHHs) specific for CD8 to track the presence of intratumoral CD8+ T cells in the immunotherapy-susceptible B16 melanoma model in response to checkpoint blockade. A 89Zr-labeled PEGylated anti-CD8 VHH detected thymus and secondary lymphoid structures as well as intratumoral CD8 T cells. Animals that responded to CTLA-4 therapy showed a homogeneous distribution of the anti-CD8 PET signal throughout the tumor, whereas more heterogeneous infiltration of CD8 T cells correlated with faster tumor growth and worse responses. To support the validity of these observations, we used two different transplantable breast cancer models, yielding results that conformed with predictions based on the antimelanoma response. It may thus be possible to use immuno-PET and monitor antitumor immune responses as a prognostic tool to predict patient responses to checkpoint therapies. © 2017 Rashidian et al.

  6. Genetic Tests To Evaluate Prognosis and Predict Therapeutic Response in Acute Myeloid Leukemia

    OpenAIRE

    Gulley, Margaret L; Shea, Thomas C.; Fedoriw, Yuri

    2010-01-01

    Management of patients with acute myeloid leukemia relies on genetic tests that inform diagnosis and prognosis, predict response to therapy, and measure minimal residual disease. The value of genetics is reinforced in the revised 2008 World Health Organization acute myeloid leukemia classification scheme. The various analytic procedures—karyotype, fluorescence in situ hybridization, reverse transcription polymerase chain reaction, DNA sequencing, and microarray technology—each have advantages...

  7. Can Ki-67 Play a Role in Prediction of Breast Cancer Patients' Response to Neoadjuvant Chemotherapy?

    Directory of Open Access Journals (Sweden)

    Juhasz-Böss Ingolf

    2014-01-01

    Full Text Available Background. Currently the choice of breast cancer therapy is based on prognostic factors. The proliferation marker Ki-67 is used increasingly to determine the method of therapy. The current study analyses the predictive value of Ki-67 in foreseeing breast cancer patients’ responses to neoadjuvant chemotherapy. Methods. This study includes patients with invasive breast cancer treated between 2008 and 2013. The clinical response was assessed by correlating Ki-67 to histological examination, mammography, and ultrasonography findings. Results. The average Ki-67 value in our patients collectively (n=77 is 34.9 ± 24.6%. The average Ki-67 value is the highest with 37.4 ± 24.0% in patients with a pCR. The Ki-67 values do not differ significantly among the 3 groups: pCR versus partial pathological response versus stable disease/progress (P=0.896. However, Ki-67 values of patients with luminal, Her2 enriched, and basal-like cancers differed significantly from each other. Furthermore, within the group of luminal tumors Ki-67 values of patients with versus without pCR also differed significantly. Conclusion. Our data shows that the Ki-67 value predicts the response to neoadjuvant chemotherapy as a function of the molecular subtype, reflecting the daily routine concerning Ki-67 and its impressing potential and limitation as a predictive marker for neoadjuvant chemotherapy response.

  8. Biomarkers of evasive resistance predict disease progression in cancer patients treated with antiangiogenic therapies

    Science.gov (United States)

    Pircher, Andreas; Jöhrer, Karin; Kocher, Florian; Steiner, Normann; Graziadei, Ivo; Heidegger, Isabel; Pichler, Renate; Leonhartsberger, Nicolai; Kremser, Christian; Kern, Johann; Untergasser, Gerold; Gunsilius, Eberhard; Hilbe, Wolfgang

    2016-01-01

    Numerous antiangiogenic agents are approved for the treatment of oncological diseases. However, almost all patients develop evasive resistance mechanisms against antiangiogenic therapies. Currently no predictive biomarker for therapy resistance or response has been established. Therefore, the aim of our study was to identify biomarkers predicting the development of therapy resistance in patients with hepatocellular cancer (n = 11), renal cell cancer (n = 7) and non-small cell lung cancer (n = 2). Thereby we measured levels of angiogenic growth factors, tumor perfusion, circulating endothelial cells (CEC), circulating endothelial progenitor cells (CEP) and tumor endothelial markers (TEM) in patients during the course of therapy with antiangiogenic agents, and correlated them with the time to antiangiogenic progression (aTTP). Importantly, at disease progression, we observed an increase of proangiogenic factors, upregulation of CEC/CEP levels and downregulation of TEMs, such as Robo4 and endothelial cell-specific chemotaxis regulator (ECSCR), reflecting the formation of torturous tumor vessels. Increased TEM expression levels tended to correlate with prolonged aTTP (ECSCR high = 275 days vs. ECSCR low = 92.5 days; p = 0.07 and for Robo4 high = 387 days vs. Robo4 low = 90.0 days; p = 0.08). This indicates that loss of vascular stabilization factors aggravates the development of antiangiogenic resistance. Thus, our observations confirm that CEP/CEC populations, proangiogenic cytokines and TEMs contribute to evasive resistance in antiangiogenic treated patients. Higher TEM expression during disease progression may have clinical and pathophysiological implications, however, validation of our results is warranted for further biomarker development. PMID:26956051

  9. Predicting maximal HR in heart failure patients on β-blockade therapy.

    Science.gov (United States)

    Keteyian, Steven J; Kitzman, Dalane; Zannad, Faiez; Landzberg, Joel; Arnold, J Malcolm; Brubaker, Peter; Brawner, Clinton A; Bensimhon, Daniel; Hellkamp, Anne S; Ewald, Greg

    2012-03-01

    Standards for estimating maximal HR are important when interpreting the adequacy of physiologic stress during exercise testing, assessing chronotropic response, and prescribing an exercise training regimen. The equation 220 - age is used to estimate maximum HR; however, it overestimates measured maximal HR in patients taking β-adrenergic blockade (βB) therapy. This study developed and validated a practical equation to predict maximal HR in patients with heart failure (HF) taking βB therapy. Data from symptom-limited exercise tests completed on patients with systolic HF participating in the Heart Failure: A Controlled Trial Investigating Outcomes of Exercise Training trial and taking a βB agent were used to develop a simplified equation, which was validated using bootstrapping. The simplified derived equation was 119 + 0.5 (resting HR) - 0.5 (age) - (0, if test was completed using a treadmill; 5, if using a stationary bike). The R2 and SEE were 0.28 and 18 beats·min(-1), respectively. Validation of this equation yielded a mean R and SEE of 0.28 and 18 beats·min(-1), respectively. For the equation 220 - age, the R2 was -2.93, and the SEE was 43 beats·min(-1). We report a valid and simple population-specific equation for estimating peak HR in patients with HF taking βB therapy. This equation should be helpful when evaluating chronotropic response or assessing if a maximum effort was provided during exercise testing. We caution, however, that the magnitude of the variation (SEE = 18 beats·min(-1)) associated with this prediction equation may make it impractical when prescribing exercise intensity.

  10. Early prediction of blonanserin response in Japanese patients with schizophrenia.

    Science.gov (United States)

    Kishi, Taro; Matsuda, Yuki; Fujita, Kiyoshi; Iwata, Nakao

    2014-01-01

    Blonanserin is a second-generation antipsychotic used for the treatment of schizophrenia in Japan and Korea. The present study aimed to examine early prediction of blonanserin in patients with schizophrenia. An 8-week, prospective, single-arm, flexible-dose clinical trial of blonanserin in patients with schizophrenia was conducted under real-world conditions. The inclusion criteria were antipsychotic naïve, and first-episode schizophrenia patients or schizophrenia patients with no consumption of any antipsychotic medication for more than 4 weeks before enrollment in this study. The positive predictive value, negative predictive value, sensitivity, specificity, and predictive power were calculated for the response status at week 4 to predict the subsequent response at week 8. Thirty-seven patients were recruited (56.8% of them had first-episode schizophrenia), and 28 (75.7%) completed the trial. At week 8, blonanserin was associated with a significant improvement in the Positive and Negative Syndrome Scale (PANSS) total score (Pblonanserin response at week 4 could predict the later response at week 8.

  11. Transcription-based prediction of response to IFNbeta using supervised computational methods.

    Directory of Open Access Journals (Sweden)

    Sergio E Baranzini

    2005-01-01

    Full Text Available Changes in cellular functions in response to drug therapy are mediated by specific transcriptional profiles resulting from the induction or repression in the activity of a number of genes, thereby modifying the preexisting gene activity pattern of the drug-targeted cell(s. Recombinant human interferon beta (rIFNbeta is routinely used to control exacerbations in multiple sclerosis patients with only partial success, mainly because of adverse effects and a relatively large proportion of nonresponders. We applied advanced data-mining and predictive modeling tools to a longitudinal 70-gene expression dataset generated by kinetic reverse-transcription PCR from 52 multiple sclerosis patients treated with rIFNbeta to discover higher-order predictive patterns associated with treatment outcome and to define the molecular footprint that rIFNbeta engraves on peripheral blood mononuclear cells. We identified nine sets of gene triplets whose expression, when tested before the initiation of therapy, can predict the response to interferon beta with up to 86% accuracy. In addition, time-series analysis revealed potential key players involved in a good or poor response to interferon beta. Statistical testing of a random outcome class and tolerance to noise was carried out to establish the robustness of the predictive models. Large-scale kinetic reverse-transcription PCR, coupled with advanced data-mining efforts, can effectively reveal preexisting and drug-induced gene expression signatures associated with therapeutic effects.

  12. Desmoid fibromatosis: MRI features of response to systemic therapy

    Energy Technology Data Exchange (ETDEWEB)

    Sheth, Pooja J.; Subhawong, Ty K. [University of Miami Miller School of Medicine/Jackson Memorial Hospital, Department of Radiology, Miami, FL (United States); Del Moral, Spencer; Wilky, Breelyn A.; Trent, Jonathan C. [University of Miami Miller School of Medicine/Sylvester Comprehensive Cancer Center, Division of Hematology/Oncology, Department of Medicine, Miami, FL (United States); Cohen, Jonathan [Oncology and Radiation Associates, Miami, FL (United States); Rosenberg, Andrew E. [University of Miami Miller School of Medicine, Department of Pathology, Miami, FL (United States); Temple, H.T. [Center for Orthopedic Innovations, Miami, FL (United States)

    2016-10-15

    Imaging criteria for measuring the response of desmoid fibromatosis to systemic therapy are not well established. We evaluated a series of patients with desmoids who underwent systemic therapy to document magnetic resonance imaging (MRI) features associated with a positive clinical response. This Institutional Review Board-approved retrospective study included 23 patients (mean age 40.5) with 29 extra-abdominal tumors. Therapeutic regimens included cytotoxic chemotherapy (n = 19), targeted therapy (n = 3), and nonsteroid anti-inflammatory drugs (NSAIDS; n = 1). Clinical effects were categorized as progressive disease, stable, or partial response. Maximum tumor dimension (D{sub max}), approximate tumor volume (V{sub Tumor}), and quantitative tumor T2 hyperintensity and contrast enhancement (relative to muscle) for pre- and post-treatment MRIs were compared. Three lesions progressed, 5 lesions were stable, whereas 21 showed a clinical response. D{sub max} decreased more in responders (mean -11.0 %) than in stable/progressive lesions (mean -3.6 and 0 % respectively, p = 0.28, ANOVA); by Response Evaluation Criteria in Solid Tumors (RECIST 1.1) 27 out of 29 lesions were ''stable,'' including the 3 progressive lesions. In responders, V{sub Tumor} change averaged -29.4 %, but -19.2 % and +32.5 % in stable and progressive lesions respectively (p = 0.002, ANOVA); by 3D criteria 14 out of 29 lesions showed a partial response. T2 hyperintensity decreased by 50-54 % in partial response/stable disease, but only by 10 % in progressive lesions (p = 0.049, t test). Changes in contrast enhancement ranged from -23 % to 0 %, but were not statistically significant among response groups (p = 0.37). Change in T2 hyperintensity showed a positive correlation with volumetric change (r = 0.40). Decreases in volume and T2 hyperintensity reflect the positive response of desmoid fibromatosis to systemic therapy; RECIST 1.1 criteria are not sensitive to clinically

  13. Can radiation therapy treatment planning system accurately predict surface doses in postmastectomy radiation therapy patients?

    Science.gov (United States)

    Wong, Sharon; Back, Michael; Tan, Poh Wee; Lee, Khai Mun; Baggarley, Shaun; Lu, Jaide Jay

    2012-01-01

    Skin doses have been an important factor in the dose prescription for breast radiotherapy. Recent advances in radiotherapy treatment techniques, such as intensity-modulated radiation therapy (IMRT) and new treatment schemes such as hypofractionated breast therapy have made the precise determination of the surface dose necessary. Detailed information of the dose at various depths of the skin is also critical in designing new treatment strategies. The purpose of this work was to assess the accuracy of surface dose calculation by a clinically used treatment planning system and those measured by thermoluminescence dosimeters (TLDs) in a customized chest wall phantom. This study involved the construction of a chest wall phantom for skin dose assessment. Seven TLDs were distributed throughout each right chest wall phantom to give adequate representation of measured radiation doses. Point doses from the CMS Xio® treatment planning system (TPS) were calculated for each relevant TLD positions and results correlated. There were no significant difference between measured absorbed dose by TLD and calculated doses by the TPS (p > 0.05 (1-tailed). Dose accuracy of up to 2.21% was found. The deviations from the calculated absorbed doses were overall larger (3.4%) when wedges and bolus were used. 3D radiotherapy TPS is a useful and accurate tool to assess the accuracy of surface dose. Our studies have shown that radiation treatment accuracy expressed as a comparison between calculated doses (by TPS) and measured doses (by TLD dosimetry) can be accurately predicted for tangential treatment of the chest wall after mastectomy. Copyright © 2012 American Association of Medical Dosimetrists. Published by Elsevier Inc. All rights reserved.

  14. Immune response genes receptors expression and polymorphisms in relation to multiple sclerosis susceptibility and response to INF-β therapy.

    Science.gov (United States)

    Karam, Rehab A; Rezk, Noha A; Amer, Mona M; Fathy, Hala A

    2016-09-01

    Interferon (IFN)-β is one of the disease modifying drugs used in the treatment of multiple sclerosis. A predictive marker that indicates good or poor response to the treatment is highly desirable. We aimed to investigate the relation between the immune response genes receptors (IFNAR1, IFNAR2, and CCR5) expression and their polymorhic variants and multiple sclerosis (MS) susceptibility as well as the response to IFN-β therapy. The immune response genes receptors expression and genotyping were analyzed in 80 patients with MS, treated with IFN-β and in 110 healthy controls. There was a significant decrease of IFNAR1 and IFNAR2 mRNA expression and a significant increase of CCR5 mRNA expression in MS patients compared with the control group. Also, the level of IFNAR1, IFNAR2, and CCR5 mRNA expression was found to be significantly lower in the responders than nonresponders. Carriers of IFNAR1 18417 C/C genotype and C allele had an increased risk of developing MS. There was a significant relation between CCR5 Δ32 allele and IFN-β treatment response in MS patients. Our results highlighted the significance of IFNAR and CCR5 genes in multiple sclerosis risk and the response to IFN-β therapy. © 2016 IUBMB Life, 68(9):727-734, 2016. © 2016 International Union of Biochemistry and Molecular Biology.

  15. Do scores on the Beck Depression Inventory-II predict outcome in cognitive processing therapy?

    Science.gov (United States)

    Asamsama, Octaviana Hemmy; Dickstein, Benjamin D; Chard, Kathleen M

    2015-09-01

    Current treatment guidelines for posttraumatic stress disorder (PTSD) recognize that severe depression may limit the effectiveness of trauma-focused interventions, making it necessary to address depression symptomatology first. However, there is a paucity of research providing specific treatment recommendations using a common depression measure like the Beck Depression Inventory-II (BDI-II). Accordingly, we examined the utility of using BDI-II cutoff scores for predicting response to cognitive processing therapy (CPT). Our sample was 757 military veterans receiving outpatient therapy at a Department of Veterans Affairs specialty clinic. At baseline, the majority of participants (58.9%) reported BDI-II scores suggestive of severe depression, and 459 (60.7%) met DSM-IV diagnostic criteria for major depressive disorder (MDD). Despite this high level of depression severity, most participants who completed therapy experienced a clinically significant reduction in symptoms (75.1%). No differences were observed across BDI-II groups on rates of clinically significant change in PTSD symptoms or on rates of treatment completion. Taken together, results suggest that CPT is an effective treatment, even in cases of severe co-occurring depression. Limitations and implications for treatment guidelines are discussed. (c) 2015 APA, all rights reserved).

  16. Individual differences in response to phantom limb movement therapy.

    Science.gov (United States)

    McAvinue, Laura P; Robertson, Ian H

    2011-01-01

    Phantom limb pain (PLP) is a distressing condition experienced by many amputees. The purpose of this study was to investigate whether motor imagery could be used to treat PLP. Four single case studies were conducted. The participants kept a pain diary in which they recorded the intensity of their PLP during a baseline period, general motor imagery training, phantom limb movement therapy and a follow-up period. Qualitative and quantitative (i.e. interrupted time series) analyses were employed to determine whether phantom limb movement therapy had a significant effect on PLP intensity. Phantom limb movement therapy significantly reduced intensity of PLP in one participant. One participant gained occasional relief by doing phantom limb movement therapy exercises but did not experience an overall reduction in PLP intensity. The third participant did not experience any relief and the fourth participant reported experiencing the re-emergence of an old pain. The results display individual differences in response to phantom limb movement therapy. Individual differences are discussed in the context of motor imagery ability and the phantom limb phenomenon as a multi-dimensional disorder.

  17. Prediction and control of neural responses to pulsatile electrical stimulation

    Science.gov (United States)

    Campbell, Luke J.; Sly, David James; O'Leary, Stephen John

    2012-04-01

    This paper aims to predict and control the probability of firing of a neuron in response to pulsatile electrical stimulation of the type delivered by neural prostheses such as the cochlear implant, bionic eye or in deep brain stimulation. Using the cochlear implant as a model, we developed an efficient computational model that predicts the responses of auditory nerve fibers to electrical stimulation and evaluated the model's accuracy by comparing the model output with pooled responses from a group of guinea pig auditory nerve fibers. It was found that the model accurately predicted the changes in neural firing probability over time to constant and variable amplitude electrical pulse trains, including speech-derived signals, delivered at rates up to 889 pulses s-1. A simplified version of the model that did not incorporate adaptation was used to adaptively predict, within its limitations, the pulsatile electrical stimulus required to cause a desired response from neurons up to 250 pulses s-1. Future stimulation strategies for cochlear implants and other neural prostheses may be enhanced using similar models that account for the way that neural responses are altered by previous stimulation.

  18. Predictive value of brain perfusion SPECT for ketamine response in hyperalgesic fibromyalgia

    Energy Technology Data Exchange (ETDEWEB)

    Guedj, Eric; Cammilleri, Serge; Colavolpe, Cecile; Taieb, David; Laforte, Catherine de; Mundler, Olivier [Centre Hospitalo-Universitaire de la Timone, Service Central de Biophysique et de Medecine Nucleaire, Assistance Publique des Hopitaux de Marseille, Marseille Cedex 5 (France); Niboyet, Jean [Clinique La Phoceanne, Unite d' Etude et de Traitement de la Douleur, Marseille (France)

    2007-08-15

    Ketamine has been used successfully in various proportions of fibromyalgia (FM) patients. However, the response to this specific treatment remains largely unpredictable. We evaluated brain SPECT perfusion before treatment with ketamine, using voxel-based analysis. The objective was to determine the predictive value of brain SPECT for ketamine response. Seventeen women with FM (48 {+-} 11 years; ACR criteria) were enrolled in the study. Brain SPECT was performed before any change was made in therapy in the pain care unit. We considered that a patient was a good responder to ketamine if the VAS score for pain decreased by at least 50% after treatment. A voxel-by-voxel group analysis was performed using SPM2, in comparison to a group of ten healthy women matched for age. The VAS score for pain was 81.8 {+-} 4.2 before ketamine and 31.8 {+-} 27.1 after ketamine. Eleven patients were considered ''good responders'' to ketamine. Responder and non-responder subgroups were similar in terms of pain intensity before ketamine. In comparison to responding patients and healthy subjects, non-responding patients exhibited a significant reduction in bilateral perfusion of the medial frontal gyrus. This cluster of hypoperfusion was highly predictive of non-response to ketamine (positive predictive value 100%, negative predictive value 91%). Brain perfusion SPECT may predict response to ketamine in hyperalgesic FM patients. (orig.)

  19. Unidentified angular recurrent ulceration responsive to antiviral therapy

    OpenAIRE

    Rahmi Amtha; Siti Aliyah Pradono

    2013-01-01

    Background: Recurrent ulcer on angular area is usually called stomatitis angularis. It is caused by many factors such as vertical dimension reduce, vitamin B12, and immune system deficiency, C. albicans and staphylococcus involvement. Clinically is characterized by painful fissure with erythematous base without fever. Purpose: to describe an unidentified angular ulcer proceeded by recurrent ulcers with no response of topical therapy. Case: An 18-years old male came to Oral Medicine clinic in ...

  20. Pareto Optimization Identifies Diverse Set of Phosphorylation Signatures Predicting Response to Treatment with Dasatinib.

    Science.gov (United States)

    Klammer, Martin; Dybowski, J Nikolaj; Hoffmann, Daniel; Schaab, Christoph

    2015-01-01

    Multivariate biomarkers that can predict the effectiveness of targeted therapy in individual patients are highly desired. Previous biomarker discovery studies have largely focused on the identification of single biomarker signatures, aimed at maximizing prediction accuracy. Here, we present a different approach that identifies multiple biomarkers by simultaneously optimizing their predictive power, number of features, and proximity to the drug target in a protein-protein interaction network. To this end, we incorporated NSGA-II, a fast and elitist multi-objective optimization algorithm that is based on the principle of Pareto optimality, into the biomarker discovery workflow. The method was applied to quantitative phosphoproteome data of 19 non-small cell lung cancer (NSCLC) cell lines from a previous biomarker study. The algorithm successfully identified a total of 77 candidate biomarker signatures predicting response to treatment with dasatinib. Through filtering and similarity clustering, this set was trimmed to four final biomarker signatures, which then were validated on an independent set of breast cancer cell lines. All four candidates reached the same good prediction accuracy (83%) as the originally published biomarker. Although the newly discovered signatures were diverse in their composition and in their size, the central protein of the originally published signature - integrin β4 (ITGB4) - was also present in all four Pareto signatures, confirming its pivotal role in predicting dasatinib response in NSCLC cell lines. In summary, the method presented here allows for a robust and simultaneous identification of multiple multivariate biomarkers that are optimized for prediction performance, size, and relevance.

  1. Characteristics influencing therapy switch behavior after suboptimal response to first-line treatment in patients with multiple sclerosis.

    Science.gov (United States)

    Teter, Barbara; Agashivala, Neetu; Kavak, Katelyn; Chouhfeh, Lynn; Hashmonay, Ron; Weinstock-Guttman, Bianca

    2014-06-01

    Factors driving disease-modifying therapy (DMT) switch behavior are not well understood. The objective of this paper is to identify patient characteristics and clinical events predictive of therapy switching in patients with suboptimal response to DMT. This retrospective study analyzed patients with relapsing-remitting multiple sclerosis (MS) and a suboptimal response to initial therapy with either interferon β or glatiramer acetate. Suboptimal responders were defined as patients with ≥1 MS event (clinical relapse, worsening disability, or MRI worsening) while on DMT. Switchers were defined as those who changed DMT within six to 12 months after the MS event. Of 606 suboptimal responders, 214 (35.3%) switched therapy. Switchers were younger at symptom onset (p = 0.012), MS diagnosis (p = 0.004), DMT initiation (p therapy switched sooner than patients who are older at the time of MS diagnosis and DMT initiation. © The Author(s) 2013.

  2. Posterior Predictive Model Checking for Multidimensionality in Item Response Theory

    Science.gov (United States)

    Levy, Roy; Mislevy, Robert J.; Sinharay, Sandip

    2009-01-01

    If data exhibit multidimensionality, key conditional independence assumptions of unidimensional models do not hold. The current work pursues posterior predictive model checking, a flexible family of model-checking procedures, as a tool for criticizing models due to unaccounted for dimensions in the context of item response theory. Factors…

  3. Predicting responsiveness to intervention in dyslexia using dynamic assessment

    NARCIS (Netherlands)

    Aravena, S.; Tijms, J.; Snellings, P.; van der Molen, M.W.

    In the current study we examined the value of a dynamic test for predicting responsiveness to reading intervention for children diagnosedwith dyslexia. The test consisted of a 20-minute training aimed at learning eight basic letter–speech sound correspondences within an artificial orthography,

  4. Prediction of Clinical Response in Children Taking Methylphenidate.

    Science.gov (United States)

    Aman, Michael G.; Turbott, Sarah H.

    1991-01-01

    Twenty-six children (ages 5-12) with attention deficit hyperactivity disorder were tested before and after treatment with methylphenidate. Few performance tests predicted clinical response to medication. Chronological age and performance on a memory distraction task and the Graduated Holes Task were moderately correlated with clinical outcome.…

  5. HER family kinase domain mutations promote tumor progression and can predict response to treatment in human breast cancer

    KAUST Repository

    Boulbes, Delphine R.

    2014-11-11

    Resistance to HER2-targeted therapies remains a major obstacle in the treatment of HER2-overexpressing breast cancer. Understanding the molecular pathways that contribute to the development of drug resistance is needed to improve the clinical utility of novel agents, and to predict the success of targeted personalized therapy based on tumor-specific mutations. Little is known about the clinical significance of HER family mutations in breast cancer. Because mutations within HER1/EGFR are predictive of response to tyrosine kinase inhibitors (TKI) in lung cancer, we investigated whether mutations in HER family kinase domains are predictive of response to targeted therapy in HER2-overexpressing breast cancer. We sequenced the HER family kinase domains from 76 HER2-overexpressing invasive carcinomas and identified 12 missense variants. Patients whose tumors carried any of these mutations did not respond to HER2 directed therapy in the metastatic setting. We developed mutant cell lines and used structural analyses to determine whether changes in protein conformation could explain the lack of response to therapy. We also functionally studied all HER2 mutants and showed that they conferred an aggressive phenotype and altered effects of the TKI lapatinib. Our data demonstrate that mutations in the finely tuned HER kinase domains play a critical function in breast cancer progression and may serve as prognostic and predictive markers.

  6. Immune regulation of therapy-resistant niches: emerging targets for improving anticancer drug responses.

    Science.gov (United States)

    Jinushi, Masahisa

    2014-09-01

    Emerging evidence has unveiled a critical role for immunological parameters in predicting tumor prognosis and clinical responses to anticancer therapeutics. On the other hand, responsiveness to anticancer drugs greatly modifies the repertoires, phenotypes, and immunogenicity of tumor-infiltrating immune cells, serving as a critical factor to regulate tumorigenic activities and the emergence of therapy-resistant phenotypes. Tumor-associated immune functions are influenced by distinct or overlapping sets of therapeutic modalities, such as cytotoxic chemotherapy, radiotherapy, or molecular-targeted therapy, and various anticancer modalities have unique properties to influence the mode of cross-talk between tumor cells and immune cells in tumor microenvironments. Thus, it is critical to understand precise molecular machineries whereby each anticancer strategy has a distinct or overlapping role in regulating the dynamism of reciprocal communication between tumor and immune cells in tumor microenvironments. Such an understanding will open new therapeutic opportunities by harnessing the immune system to overcome resistance to conventional anticancer drugs.

  7. The prediction and measurement of microdosimetric spectra relating to neutron cancer therapy

    CERN Document Server

    Taylor, G C

    2003-01-01

    The primary aim of this work has been to characterise the beam of the MRC's high energy neutron cancer therapy cyclotron at the Clatterbridge Hospital, Bebington, the Wirral, by measuring a series of microdosimetric spectra for a variety of irradiation conditions. In order to interpret the variation between these spectra, so that the underlying physics of the neutron beam could be determined, it was necessary to identify the most influential factors in the production of microdosimetric responses. Experimental procedures were tested in a series of measurements using 14 and 15 MeV monoenergetic neutrons from the Birmingham Dynamitron; these were instrumental in establishing the rigorous calibration regime necessary for the Clatterbridge measurement programme. The (analytical) predictive code NESLES was used to investigate the effect on microdosimetric spectra of having a low energy neutron component in the primary beam,, and also to highlight the shortcomings of the tissue-equivalent media used in microdosimetr...

  8. A prediction model for the response to oral labetalol for the treatment of antenatal hypertension.

    Science.gov (United States)

    Stott, D; Bolten, M; Salman, M; Paraschiv, D; Douiri, A; Kametas, N A

    2017-02-01

    This prospective observational study aimed to identify at presentation the maternal hemodynamic and demographic variables associated with a therapeutic response to oral labetalol and to use these variables to develop a prediction model to anticipate the response to labetalol monotherapy in women with hypertension. It was set at a maternity unit in a UK teaching hospital. Maternal demographic data from 50 pregnant women, presenting with hypertension between January and August 2013, was collected and blood pressure measured with a device validated for pregnancy and pre-eclampsia. Maternal haemodynamics were assessed with a bioreactance monitor. Participants were commenced on oral labetalol, and reviewed until delivery and discharge home. Logistic regression analysis was performed to assess the prediction of response to labetalol according to the maternal demographic and hemodynamic variables. Main outcome measures were the response to labetalol monotherapy up to delivery and discharge home, defined as sustained blood pressure control labetalol monotherapy, 13 (26%) failed to achieve control with labetalol alone, of whom 9 developed severe hypertension. Multivariate logistic regression showed that heart rate, ethnicity and stroke volume index were independent predictors of the response to labetalol. The predictive accuracy of the model was 96% (95% confidence interval (CI) 86-99%). Maternal demographics and haemodynamics are potent predictors for the response to labetalol, and these parameters may guide therapy to enable effective blood pressure control and a lowering of severe hypertension rates.

  9. Serum metabolites predict response to angiotensin II receptor blockers in patients with diabetes mellitus.

    Science.gov (United States)

    Pena, Michelle J; Heinzel, Andreas; Rossing, Peter; Parving, Hans-Henrik; Dallmann, Guido; Rossing, Kasper; Andersen, Steen; Mayer, Bernd; Heerspink, Hiddo J L

    2016-07-05

    Individual patients show a large variability in albuminuria response to angiotensin receptor blockers (ARB). Identifying novel biomarkers that predict ARB response may help tailor therapy. We aimed to discover and validate a serum metabolite classifier that predicts albuminuria response to ARBs in patients with diabetes mellitus and micro- or macroalbuminuria. Liquid chromatography-tandem mass spectrometry metabolomics was performed on serum samples. Data from patients with type 2 diabetes and microalbuminuria (n = 49) treated with irbesartan 300 mg/day were used for discovery. LASSO and ridge regression were performed to develop the classifier. Improvement in albuminuria response prediction was assessed by calculating differences in R(2) between a reference model of clinical parameters and a model with clinical parameters and the classifier. The classifier was externally validated in patients with type 1 diabetes and macroalbuminuria (n = 50) treated with losartan 100 mg/day. Molecular process analysis was performed to link metabolites to molecular mechanisms contributing to ARB response. In discovery, median change in urinary albumin excretion (UAE) was -42 % [Q1-Q3: -69 to -8]. The classifier, consisting of 21 metabolites, was significantly associated with UAE response to irbesartan (p diabetes mellitus.

  10. Response-driven Imaging Biomarkers for Predicting Radiation Necrosis of the Brain

    Science.gov (United States)

    Nazem-Zadeh, Mohammad-Reza; Chapman, Christopher H.; Chenevert, Thomas; Lawrence, Theodore S.; Ten Haken, Randall K.; Tsien, Christina I.; Cao, Yue

    2014-01-01

    Purpose Radiation necrosis is an uncommon but severe adverse effect of brain radiation therapy. Current predictive models based on radiation dose have limited accuracy. We aimed to identify early individual response biomarkers based upon diffusion tensor (DT) imaging and incorporated them into a response model for prediction of radiation necrosis. Methods and Materials Twenty-nine patients with glioblastoma received six weeks of intensity modulated radiation therapy (RT) and concurrent temozolamide. Patients underwent DT-MRI scans before treatment, at three weeks during RT, and one, three, and six months after RT. Cases with radiation necrosis were classified based on generalized equivalent uniform dose (gEUD) of whole brain and DT index early changes in the corpus callosum and its substructures. Significant covariates were used to develop normal tissue complication probability models using binary logistic regression. Results Seven patients developed radiation necrosis. Percentage changes of radial diffusivity (RD) in the splenium at three weeks during RT and at six months after RT differed significantly between the patients with and without necrosis (p=0.05 and p=0.01). Percentage change of RD at three weeks during RT in the 30 Gy dose-volume of the splenium and brain gEUD combined yielded the best-fit logistic regression model. Conclusions Our findings indicate that early individual response during the course of RT, assessed by radial diffusivity, has the potential to aid in predicting delayed radiation necrosis, which could provide guidance in dose-escalation trials. PMID:24778364

  11. Predicting Treatment Success in Child and Parent Therapy Among Families in Poverty.

    Science.gov (United States)

    Mattek, Ryan J; Harris, Sara E; Fox, Robert A

    2016-01-01

    Behavior problems are prevalent in young children and those living in poverty are at increased risk for stable, high-intensity behavioral problems. Research has demonstrated that participation in child and parent therapy (CPT) programs significantly reduces problematic child behaviors while increasing positive behaviors. However, CPT programs, particularly those implemented with low-income populations, frequently report high rates of attrition (over 50%). Parental attributional style has shown some promise as a contributing factor to treatment attendance and termination in previous research. The authors examined if parental attributional style could predict treatment success in a CPT program, specifically targeting low-income urban children with behavior problems. A hierarchical logistic regression was used with a sample of 425 families to assess if parent- and child-referent attributions variables predicted treatment success over and above demographic variables and symptom severity. Parent-referent attributions, child-referent attributions, and child symptom severity were found to be significant predictors of treatment success. Results indicated that caregivers who viewed themselves as a contributing factor for their child's behavior problems were significantly more likely to demonstrate treatment success. Alternatively, caregivers who viewed their child as more responsible for their own behavior problems were less likely to demonstrate treatment success. Additionally, more severe behavior problems were also predictive of treatment success. Clinical and research implications of these results are discussed.

  12. The Pupillary Orienting Response Predicts Adaptive Behavioral Adjustment after Errors.

    Directory of Open Access Journals (Sweden)

    Peter R Murphy

    Full Text Available Reaction time (RT is commonly observed to slow down after an error. This post-error slowing (PES has been thought to arise from the strategic adoption of a more cautious response mode following deployment of cognitive control. Recently, an alternative account has suggested that PES results from interference due to an error-evoked orienting response. We investigated whether error-related orienting may in fact be a pre-cursor to adaptive post-error behavioral adjustment when the orienting response resolves before subsequent trial onset. We measured pupil dilation, a prototypical measure of autonomic orienting, during performance of a choice RT task with long inter-stimulus intervals, and found that the trial-by-trial magnitude of the error-evoked pupil response positively predicted both PES magnitude and the likelihood that the following response would be correct. These combined findings suggest that the magnitude of the error-related orienting response predicts an adaptive change of response strategy following errors, and thereby promote a reconciliation of the orienting and adaptive control accounts of PES.

  13. Prenatal Cortisol Exposure Predicts Infant Cortisol Response to Acute Stress

    Science.gov (United States)

    O’Connor, Thomas G; Bergman, Kristin; Sarkar, Pampa; Glover, Vivette

    2012-01-01

    Summary Experimental animal findings suggest that early stress and glucocorticoid exposure may program the function of the Hypothalamic-pituitary-adrenal (HPA) axis in the offspring. The extension of these findings to human development is not yet clear. A prospective longitudinal study was conducted on 125 mothers and their normally developing children. Amniotic fluid was obtained at, on average, 17.2 weeks gestation; infant behavior and cortisol response to a separation-reunion stress was assessed at 17 months. Amniotic fluid cortisol predicted infant cortisol response to separation-reunion stress: infants who were exposed to higher levels of cortisol in utero showed higher pre-stress cortisol values and blunted response to stress exposure. The association was independent of prenatal, obstetric, and socioeconomic factors and child-parent attachment. The findings provide some of the strongest data in humans that HPA axis functioning in the child may be predicted from prenatal cortisol exposure. PMID:22315044

  14. Pittsburgh Response to Endovascular therapy (PRE) score: optimizing patient selection for endovascular therapy for large vessel occlusion strokes.

    Science.gov (United States)

    Rangaraju, Srikant; Aghaebrahim, Amin; Streib, Christopher; Sun, Chung-Huan; Ribo, Marc; Muchada, Marion; Nogueira, Raul; Frankel, Michael; Gupta, Rishi; Jadhav, Ashutosh; Jovin, Tudor G

    2015-11-01

    Endovascular therapy seems to benefit a subset of patients with large vessel occlusion strokes. We aimed to develop a clinically useful tool to identify patients who are likely to benefit from endovascular therapy. In a derivation cohort of consecutively treated patients with anterior circulation large vessel occlusion (Grady Memorial Hospital, N=247), independent predictors (pPittsburgh Response to Endovascular therapy (PRE) score as a predictor of good outcome. The PRE score was validated in two institutional cohorts (University of Pittsburgh Medical Center (UPMC): N=393; Unitat d'Ictus Vall d'Hebron: N=204) and its discriminative power for good outcome was compared with other validated tools. Benefit of successful recanalization was assessed in PRE score groups. Independent predictors of good outcome in the derivation cohort (age, baseline National Institute of Health Stroke Scale (NIHSS) score and Alberta Stroke Program Early CT Score (ASPECTS)) were used in the model: PRE score=age (years)+2×NIHSS-10 × ASPECTS. PRE score was highly predictive of good outcome in the derivation cohort (area under the curve (AUC)=0.79) and validation cohorts (UPMC: AUC=0.79; UIVH: AUC=0.72) with comparable rates of good outcome in all PRE risk quartiles. PRE was superior to Totaled Health Risks In Vascular Events (THRIVE) (p=0.03) and Stroke Prognostication using Age and NIHSS (SPAN) (p=0.007), with a trend towards superiority to Houston Intra-Arterial Therapy 2 (HIAT2) (p=0.06) and iSCORE (p=0.051) in predicting good outcomes. Better outcomes were associated with successful recanalization in patients with PRE scores -24 to +49 but not in patients with PRE scores <-24 or ≥ 50. The PRE score is a validated tool that predicts outcomes and may facilitate patient selection for endovascular therapy in anterior circulation large vessel occlusions. 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.

  15. TS Gene Polymorphisms Are Not Good Markers of Response to 5-FU Therapy in Stage III Colon Cancer Patients

    Directory of Open Access Journals (Sweden)

    A. Fariña-Sarasqueta

    2010-01-01

    Full Text Available Aim: Although the predictive and prognostic value of thymidylate synthase (TS expression and gene polymorphism in colon cancer has been widely studied, the results are inconclusive probably because of methodological differences. With this study, we aimed to elucidate the role of TS gene polymorphisms genotyping in therapy response in stage III colon carcinoma patients treated with 5-FU adjuvant chemotherapy.

  16. Early prediction of blonanserin response in Japanese patients with schizophrenia

    Directory of Open Access Journals (Sweden)

    Kishi T

    2014-09-01

    Full Text Available Taro Kishi,1 Yuki Matsuda,1 Kiyoshi Fujita,2,3 Nakao Iwata1 1Department of Psychiatry, Fujita Health University School of Medicine, Toyoake, Aichi, Japan; 2Department of Psychiatry, Okehazama Hospital, Toyoake, Aichi, Japan; 3The Neuroscience Research Center, Toyoake, Aichi, Japan Background: Blonanserin is a second-generation antipsychotic used for the treatment of schizophrenia in Japan and Korea. The present study aimed to examine early prediction of blonanserin in patients with schizophrenia. Methods: An 8-week, prospective, single-arm, flexible-dose clinical trial of blonanserin in patients with schizophrenia was conducted under real-world conditions. The inclusion criteria were antipsychotic naïve, and first-episode schizophrenia patients or schizophrenia patients with no consumption of any antipsychotic medication for more than 4 weeks before enrollment in this study. The positive predictive value, negative predictive value, sensitivity, specificity, and predictive power were calculated for the response status at week 4 to predict the subsequent response at week 8.Results: Thirty-seven patients were recruited (56.8% of them had first-episode schizophrenia, and 28 (75.7% completed the trial. At week 8, blonanserin was associated with a significant improvement in the Positive and Negative Syndrome Scale (PANSS total score (P<0.0001 and in positive (P<0.0001, negative (P<0.0001, and general subscale scores (P<0.0001. In terms of percentage improvement of PANSS total scores from baseline to week 8, 64.9% of patients showed a ≥20% reduction in the PANSS total score and 48.6% showed a ≥30% reduction. However, 8.1% of patients experienced at least one adverse event. Using the 20% reduction in the PANSS total score at week 4 as a definition of an early response, the negative predictive values for later responses (ie, reductions of ≥30 and ≥40 in the PANSS total scores were 88.9% and 94.1%, respectively. The specificities were 80.0% and

  17. Age moderates response to acceptance and commitment therapy vs. cognitive behavioral therapy for chronic pain.

    Science.gov (United States)

    Wetherell, Julie Loebach; Petkus, Andrew J; Alonso-Fernandez, Miriam; Bower, Emily S; Steiner, Amanda R W; Afari, Niloofar

    2016-03-01

    The purpose of this study was to examine age differences in response to different forms of psychotherapy for chronic pain. We performed a secondary analysis of 114 adults (ages 18-89 years) with a variety of chronic, nonmalignant pain conditions randomly assigned to 8 weeks of group-administered acceptance and commitment therapy (ACT) or cognitive behavioral therapy (CBT). Treatment response was defined as a drop of at least three points on the Brief Pain Inventory-interference subscale. Older adults were more likely to respond to ACT, and younger adults to CBT, both immediately following treatment and at 6-month follow-up. There were no significant differences in credibility, expectations of positive outcome, attrition, or satisfaction, although there was a trend for the youngest adults (ages 18-45 years) to complete fewer sessions. These data suggest that ACT may be an effective and acceptable treatment for chronic pain in older adults. Copyright © 2015 John Wiley & Sons, Ltd.

  18. Theory and Practice of Positive Feminist Therapy: A Culturally Responsive Approach to Divorce Therapy with Chinese Women

    Science.gov (United States)

    Tzou, Jean Yuh-Jin; Kim, Eunha; Waldheim, Kim

    2012-01-01

    Positive Feminist Therapy (PFT) is a strength-based culturally responsive therapy model specifically designed for helping Chinese women facing marital conflicts and divorce, integrating Empowerment Feminist Therapy, systems theory, and positive psychology. To help clients become change agents, PFT uses clients' existing strengths to develop…

  19. Predicting the Toxicity of Adjuvant Breast Cancer Drug Combination Therapy

    Science.gov (United States)

    2013-03-01

    Combination With Trastuzumab in Patients With HER2-Positive, Metastatic Breast Cancer Recruiting No Results Available NO Drug: Lapatinib|Drug: Herceptin ...Trastuzumab ( Herceptin ) -Refractory, Metastatic Breast Cancer Active, not recruiting No Results Available NO Drug: Capecitabine|Drug: Lapatinib Lapatinib...Lapatinib Plus Herceptin With or Without Endocrine Therapy Recruiting No Results Available NO Drug: Herceptin |Drug: Lapatinib|Drug: Letrozole

  20. Emotional responses to music: towards scientific perspectives on music therapy.

    Science.gov (United States)

    Suda, Miyuki; Morimoto, Kanehisa; Obata, Akiko; Koizumi, Hideaki; Maki, Atsushi

    2008-01-08

    Neurocognitive research has the potential to identify the relevant effects of music therapy. In this study, we examined the effect of music mode (major vs. minor) on stress reduction using optical topography and an endocrinological stress marker. In salivary cortisol levels, we observed that stressful conditions such as mental fatigue (thinking and creating a response) was reduced more by major mode music than by minor mode music. We suggest that music specifically induces an emotional response similar to a pleasant experience or happiness. Moreover, we demonstrated the typical asymmetrical pattern of stress responses in upper temporal cortex areas, and suggested that happiness/sadness emotional processing might be related to stress reduction by music.

  1. The evolution of the major hepatitis C genotypes correlates with clinical response to interferon therapy.

    Directory of Open Access Journals (Sweden)

    Phillip S Pang

    2009-08-01

    Full Text Available Patients chronically infected with hepatitis C virus (HCV require significantly different durations of therapy and achieve substantially different sustained virologic response rates to interferon-based therapies, depending on the HCV genotype with which they are infected. There currently exists no systematic framework that explains these genotype-specific response rates. Since humans are the only known natural hosts for HCV-a virus that is at least hundreds of years old-one possibility is that over the time frame of this relationship, HCV accumulated adaptive mutations that confer increasing resistance to the human immune system. Given that interferon therapy functions by triggering an immune response, we hypothesized that clinical response rates are a reflection of viral evolutionary adaptations to the immune system.We have performed the first phylogenetic analysis to include all available full-length HCV genomic sequences (n = 345. This resulted in a new cladogram of HCV. This tree establishes for the first time the relative evolutionary ages of the major HCV genotypes. The outcome data from prospective clinical trials that studied interferon and ribavirin therapy was then mapped onto this new tree. This mapping revealed a correlation between genotype-specific responses to therapy and respective genotype age. This correlation allows us to predict that genotypes 5 and 6, for which there currently are no published prospective trials, will likely have intermediate response rates, similar to genotype 3. Ancestral protein sequence reconstruction was also performed, which identified the HCV proteins E2 and NS5A as potential determinants of genotype-specific clinical outcome. Biochemical studies have independently identified these same two proteins as having genotype-specific abilities to inhibit the innate immune factor double-stranded RNA-dependent protein kinase (PKR.An evolutionary analysis of all available HCV genomes supports the hypothesis

  2. QRS frequency characteristics help predict response to cardiac resynchronization in left bundle branch block less than 150 milliseconds.

    Science.gov (United States)

    Niebauer, Mark J; Rickard, John; Polakof, Landon; Tchou, Patrick J; Varma, Niraj

    2014-12-01

    Baseline QRS duration (QRSd) ≥150 ms is a recognized predictor of clinical improvement by cardiac resynchronization therapy (CRT), particularly for those with left bundle branch (LBBB). Patients with QRSd 52% below 10 Hz was especially predictive of response in those with QRSd <150 ms. In these patients, this power threshold was highly predictive of CRT response (positive predictive value 85.7%, negative predictive value 71.4%). In this group of CRT recipients with LBBB, retrospective analysis of QRS frequency content below 10 Hz had greater predictive value for CRT response than baseline QRSd, particularly in those with QRSd <150 ms. Copyright © 2014 Heart Rhythm Society. Published by Elsevier Inc. All rights reserved.

  3. Predictors of response and drop-out during intensive dialectical behavior therapy.

    Science.gov (United States)

    Perroud, Nader; Uher, Rudolf; Dieben, Karen; Nicastro, Rosetta; Huguelet, Philippe

    2010-10-01

    The purpose of this study was to examine the effectiveness, and predictors of response and drop-out during a four-week course of intensive dialectical behavior therapy (I-DBT) in 447 outpatients suffering from borderline personality disorder (BPD), over a 10-year period. Assessments included a diagnostic interview, the International Personality Disorder Examination Screening Questionnaire, the Beck Depression Inventory, and the Beck Hopelessness Scale. Among these participants, 103 started a second course of treatment. In agreement with previous reports, I-DBT was effective in reducing levels of depression and hopelessness with a trend of increasing effectiveness over the study period. High schizoid scores and low narcissistic score predicted poor response. Treatment completion rate was high, and low education predicted dropout. A discussion on the usefulness of a second course of treatment should be held with patients and staff as it was not effective in reducing depression and hopelessness.

  4. Metabolic response at repeat PET/CT predicts pathological response to neoadjuvant chemotherapy in oesophageal cancer

    Energy Technology Data Exchange (ETDEWEB)

    Gillies, R.S. [Oxford Cancer and Haematology Centre, Department of Oncology, Oxford (United Kingdom); Oxford Cancer and Haematology Centre, Department of Oesophagogastric Surgery, Oxford (United Kingdom); NIHR Biomedical Research Centre, Oxford (United Kingdom); Middleton, M.R. [Oxford Cancer and Haematology Centre, Department of Oncology, Oxford (United Kingdom); NIHR Biomedical Research Centre, Oxford (United Kingdom); Blesing, C.; Patel, K.; Warner, N. [Oxford Cancer and Haematology Centre, Department of Oncology, Oxford (United Kingdom); Marshall, R.E.K.; Maynard, N.D. [Oxford Cancer and Haematology Centre, Department of Oesophagogastric Surgery, Oxford (United Kingdom); Bradley, K.M. [Oxford Cancer and Haematology Centre, Department of Radiology, Oxford (United Kingdom); Gleeson, F.V. [Oxford Cancer and Haematology Centre, Department of Radiology, Oxford (United Kingdom); NIHR Biomedical Research Centre, Oxford (United Kingdom)

    2012-09-15

    Reports have suggested that a reduction in tumour 18F-fluorodeoxyglucose (FDG) uptake on positron emission tomography (PET) examination during or after neoadjuvant chemotherapy may predict pathological response in oesophageal cancer. Our aim was to determine whether metabolic response predicts pathological response to a standardised neoadjuvant chemotherapy regimen within a prospective clinical trial. Consecutive patients staged with potentially curable oesophageal cancer who underwent treatment within a non-randomised clinical trial were included. A standardised chemotherapy regimen (two cycles of oxaliplatin and 5-fluorouracil) was used. PET/CT was performed before chemotherapy and repeated 24-28 days after the start of cycle 2. Forty-eight subjects were included: mean age 65 years; 37 male. Using the median percentage reduction in SUV{sub max} (42%) to define metabolic response, pathological response was seen in 71% of metabolic responders (17/24) compared with 33% of non-responders (8/24; P = 0.009, sensitivity 68%, specificity 70%). Pathological response was seen in 81% of subjects with a complete metabolic response (13/16) compared with 38% of those with a less than complete response (12/32; P = 0.0042, sensitivity 52%, specificity 87%). There was no significant histology-based effect. There was a significant association between metabolic response and pathological response; however, accuracy in predicting pathological response was relatively low. (orig.)

  5. Predicting the safety and efficacy of buffer therapy to raise tumour pHe: an integrative modelling study.

    Science.gov (United States)

    Martin, N K; Robey, I F; Gaffney, E A; Gillies, R J; Gatenby, R A; Maini, P K

    2012-03-27

    Clinical positron emission tomography imaging has demonstrated the vast majority of human cancers exhibit significantly increased glucose metabolism when compared with adjacent normal tissue, resulting in an acidic tumour microenvironment. Recent studies demonstrated reducing this acidity through systemic buffers significantly inhibits development and growth of metastases in mouse xenografts. We apply and extend a previously developed mathematical model of blood and tumour buffering to examine the impact of oral administration of bicarbonate buffer in mice, and the potential impact in humans. We recapitulate the experimentally observed tumour pHe effect of buffer therapy, testing a model prediction in vivo in mice. We parameterise the model to humans to determine the translational safety and efficacy, and predict patient subgroups who could have enhanced treatment response, and the most promising combination or alternative buffer therapies. The model predicts a previously unseen potentially dangerous elevation in blood pHe resulting from bicarbonate therapy in mice, which is confirmed by our in vivo experiments. Simulations predict limited efficacy of bicarbonate, especially in humans with more aggressive cancers. We predict buffer therapy would be most effectual: in elderly patients or individuals with renal impairments; in combination with proton production inhibitors (such as dichloroacetate), renal glomular filtration rate inhibitors (such as non-steroidal anti-inflammatory drugs and angiotensin-converting enzyme inhibitors), or with an alternative buffer reagent possessing an optimal pK of 7.1-7.2. Our mathematical model confirms bicarbonate acts as an effective agent to raise tumour pHe, but potentially induces metabolic alkalosis at the high doses necessary for tumour pHe normalisation. We predict use in elderly patients or in combination with proton production inhibitors or buffers with a pK of 7.1-7.2 is most promising.

  6. Baseline MELD Score Predicts Hepatic Decompensation during Antiviral Therapy in Patients with Chronic Hepatitis C and Advanced Cirrhosis

    Science.gov (United States)

    Dultz, Georg; Seelhof, Martin; Herrmann, Eva; Welker, Martin-Walter; Friedrich-Rust, Mireen; Teuber, Gerlinde; Kronenberger, Bernd; von Wagner, Michael; Vermehren, Johannes; Sarrazin, Christoph; Zeuzem, Stefan; Hofmann, Wolf Peter

    2013-01-01

    Background and Aims In patients with advanced liver cirrhosis due to chronic hepatitis C virus (HCV) infection antiviral therapy with peginterferon and ribavirin is feasible in selected cases only due to potentially life-threatening side effects. However, predictive factors associated with hepatic decompensation during antiviral therapy are poorly defined. Methods In a retrospective cohort study, 68 patients with HCV-associated liver cirrhosis (mean MELD score 9.18±2.72) were treated with peginterferon and ribavirin. Clinical events indicating hepatic decompensation (onset of ascites, hepatic encephalopathy, upper gastrointestinal bleeding, hospitalization) as well as laboratory data were recorded at baseline and during a follow up period of 72 weeks after initiation of antiviral therapy. To monitor long term sequelae of end stage liver disease an extended follow up for HCC development, transplantation and death was applied (240weeks, ±SD 136weeks). Results Eighteen patients (26.5%) achieved a sustained virologic response. During the observational period a hepatic decompensation was observed in 36.8%. Patients with hepatic decompensation had higher MELD scores (10.84 vs. 8.23, p14, respectively. Baseline MELD score was significantly associated with the risk for transplantation/death (p<0.001). Conclusions Our data suggest that the baseline MELD score predicts the risk of hepatic decompensation during antiviral therapy and thus contributes to decision making when antiviral therapy is discussed in HCV patients with advanced liver cirrhosis. PMID:23936497

  7. Baseline MELD score predicts hepatic decompensation during antiviral therapy in patients with chronic hepatitis C and advanced cirrhosis.

    Directory of Open Access Journals (Sweden)

    Georg Dultz

    Full Text Available In patients with advanced liver cirrhosis due to chronic hepatitis C virus (HCV infection antiviral therapy with peginterferon and ribavirin is feasible in selected cases only due to potentially life-threatening side effects. However, predictive factors associated with hepatic decompensation during antiviral therapy are poorly defined.In a retrospective cohort study, 68 patients with HCV-associated liver cirrhosis (mean MELD score 9.18 ± 2.72 were treated with peginterferon and ribavirin. Clinical events indicating hepatic decompensation (onset of ascites, hepatic encephalopathy, upper gastrointestinal bleeding, hospitalization as well as laboratory data were recorded at baseline and during a follow up period of 72 weeks after initiation of antiviral therapy. To monitor long term sequelae of end stage liver disease an extended follow up for HCC development, transplantation and death was applied (240 weeks, ± SD 136 weeks.Eighteen patients (26.5% achieved a sustained virologic response. During the observational period a hepatic decompensation was observed in 36.8%. Patients with hepatic decompensation had higher MELD scores (10.84 vs. 8.23, p14, respectively. Baseline MELD score was significantly associated with the risk for transplantation/death (p<0.001.Our data suggest that the baseline MELD score predicts the risk of hepatic decompensation during antiviral therapy and thus contributes to decision making when antiviral therapy is discussed in HCV patients with advanced liver cirrhosis.

  8. Response-predictive gene expression profiling of glioma progenitor cells in vitro.

    Directory of Open Access Journals (Sweden)

    Sylvia Moeckel

    Full Text Available High-grade gliomas are amongst the most deadly human tumors. Treatment results are disappointing. Still, in several trials around 20% of patients respond to therapy. To date, diagnostic strategies to identify patients that will profit from a specific therapy do not exist.In this study, we used serum-free short-term treated in vitro cell cultures to predict treatment response in vitro. This approach allowed us (a to enrich specimens for brain tumor initiating cells and (b to confront cells with a therapeutic agent before expression profiling.As a proof of principle we analyzed gene expression in 18 short-term serum-free cultures of high-grade gliomas enhanced for brain tumor initiating cells (BTIC before and after in vitro treatment with the tyrosine kinase inhibitor Sunitinib. Profiles from treated progenitor cells allowed to predict therapy-induced impairment of proliferation in vitro.For the tyrosine kinase inhibitor Sunitinib used in this dataset, the approach revealed additional predictive information in comparison to the evaluation of classical signaling analysis.

  9. Using biomarkers to predict treatment response in major depressive disorder: evidence from past and present studies.

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    Thase, Michael E

    2014-12-01

    Major depressive disorder (MDD) is a heterogeneous condition with a variable response to a wide range of treatments. Despite intensive efforts, no biomarker has been identified to date that can reliably predict response or non-response to any form of treatment, nor has one been identified that can be used to identify those at high risk of developing treatment-resistant depression (ie, non-response to a sequence of treatments delivered for adequate duration and intensity). This manuscript reviews some past areas of research that have proved informative, such as studies using indexes of hypercortisolism or sleep disturbance, and more recent research findings using measures of inflammation and different indicators of regional cortical activation to predict treatment response. It is concluded that, although no method has yet been demonstrated to be sufficiently accurate to be applied in clinical practice, progress has been made. It thus seems likely that--at some point in the not-too-distant future--it will be possible to prospectively identify, at least for some MDD patients, the likelihood of response or non-response to cognitive therapy or various antidepressant medications.

  10. Prediction of anti-cancer drug response by kernelized multi-task learning.

    Science.gov (United States)

    Tan, Mehmet

    2016-10-01

    Chemotherapy or targeted therapy are two of the main treatment options for many types of cancer. Due to the heterogeneous nature of cancer, the success of the therapeutic agents differs among patients. In this sense, determination of chemotherapeutic response of the malign cells is essential for establishing a personalized treatment protocol and designing new drugs. With the recent technological advances in producing large amounts of pharmacogenomic data, in silico methods have become important tools to achieve this aim. Data produced by using cancer cell lines provide a test bed for machine learning algorithms that try to predict the response of cancer cells to different agents. The potential use of these algorithms in drug discovery/repositioning and personalized treatments motivated us in this study to work on predicting drug response by exploiting the recent pharmacogenomic databases. We aim to improve the prediction of drug response of cancer cell lines. We propose to use a method that employs multi-task learning to improve learning by transfer, and kernels to extract non-linear relationships to predict drug response. The method outperforms three state-of-the-art algorithms on three anti-cancer drug screen datasets. We achieved a mean squared error of 3.305 and 0.501 on two different large scale screen data sets. On a recent challenge dataset, we obtained an error of 0.556. We report the methodological comparison results as well as the performance of the proposed algorithm on each single drug. The results show that the proposed method is a strong candidate to predict drug response of cancer cell lines in silico for pre-clinical studies. The source code of the algorithm and data used can be obtained from http://mtan.etu.edu.tr/Supplementary/kMTrace/. Copyright © 2016 Elsevier B.V. All rights reserved.

  11. MRI evaluation of anterior knee pain: predicting response to nonoperative treatment

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    Wittstein, Jocelyn R.; Garrett, William E. [Duke University Medical Center, Division of Orthopaedic Surgery, Durham, NC (United States); O' Brien, Seth D. [Brooke Army Medical Center, Department of Radiology, San Antonio, TX (United States); Vinson, Emily N. [Duke University Medical Center, Department of Radiology, Durham, NC (United States)

    2009-09-15

    Tibial tubercle lateral deviation and patellofemoral chondromalacia are associated with anterior knee pain (AKP). We hypothesized that increased tibial tubercle lateral deviation and patellofemoral chondromalacia on magnetic resonance imaging correlates with the presence of AKP and with failure of nonoperative management. In this retrospective comparative study, a blinded musculoskeletal radiologist measured tibial tubercle lateral deviation relative to the trochlear groove in 15 controls, 15 physical therapy responders with AKP, and 15 physical therapy nonresponders with AKP. Patellar and trochlear cartilage was assessed for signal abnormality, irregularity, and defects. The mean tibial tubercle lateral deviation in controls, physical therapy responders, and physical therapy nonresponders were 9.32 {+-} 0.68, 13.01 {+-} 0.82, and 16.07 {+-} 1.16 mm, respectively (data are mean {+-} standard deviation). The correlation coefficients for tubercle deviation, chondromalacia patellae, and trochlear chondromalacia were 0.51 (P < 0.01), 0.44 (P < 0.01), and 0.28 (P < 0.05), respectively. On analysis of variance, tubercle deviation and chondromalacia patellae contributed significantly to prediction of AKP and response to physical therapy. The presence of chondromalacia patellae and a tubercle deviation greater than 14.6 mm is 100% specific and 67% sensitive with a positive predictive value of 100% and negative predictive value of 75% for failure of nonoperative management. Subjects with AKP have more laterally positioned tibial tubercles and are more likely to have patellar chondromalacia. Patients with AKP, chondromalacia patellae, and a tubercle deviation greater than 14.6 mm are unlikely to respond to nonoperative treatment. Knowledge of tibial tubercle lateralization and presence of chondromalacia patellae may assist clinicians in determining patient prognosis and selecting treatment options. (orig.)

  12. Prediction of effect of pegylated interferon alpha-2b plus ribavirin combination therapy in patients with chronic hepatitis C infection.

    Directory of Open Access Journals (Sweden)

    Tetsuro Takayama

    Full Text Available Treatment with pegylated interferon alpha-2b (PEGIFN plus ribavirin (RBV is standard therapy for patients with chronic hepatitis C. Although the effectiveness, patients with high titres of group Ib hepatitis C virus (HCV respond poorly compared to other genotypes. At present, we cannot predict the effect in an individual. Previous studies have used traditional statistical analysis by assuming a linear relationship between clinical features, but most phenomena in the clinical situation are not linearly related. The aim of this study is to predict the effect of PEG IFN plus RBV therapy on an individual patient level using an artificial neural network system (ANN. 156 patients with HCV group 1b from multiple centres were treated with PEGIFN (1.5 µg/kg plus RBV (400-1000 mg for 48 weeks. Data on the patients' demographics, laboratory tests, PEGIFN, and RBV doses, early viral responses (EVR, and sustained viral responses were collected. Clinical data were randomly divided into training data set and validation data set and analyzed using multiple logistic regression analysis (MLRs and ANN to predict individual outcomes. The sensitivities of predictive expression were 0.45 for the MLRs models and 0.82 for the ANNs and specificities were 0.55 for the MLR and 0.88 for the ANN. Non-linear relation analysis showed that EVR, serum creatinine, initial dose of Ribavirin, gender and age were important predictive factors, suggesting non-linearly related to outcome. In conclusion, ANN was more accurate than MLRs in predicting the outcome of PEGIFN plus RBV therapy in patients with group 1b HCV.

  13. Parametric response mapping of dynamic CT for predicting intrahepatic recurrence of hepatocellular carcinoma after conventional transcatheter arterial chemoembolization

    Energy Technology Data Exchange (ETDEWEB)

    Choi, Seung Joon; Kim, Hyung Sik [Gachon University Gil Hospital, Department of Radiology, Incheon (Korea, Republic of); Kim, Jonghoon [Sungkyunkwan University, Department of Electronic Electrical and Computer Engineering, Suwon (Korea, Republic of); Seo, Jongbum [Yonsei University, Department of Biomedical Engineering, Wonju (Korea, Republic of); Lee, Jong-min [Hanyang University, Department of Biomedical Engineering, Seoul (Korea, Republic of); Park, Hyunjin [Sungkyunwkan University, School of Electronic and Electrical Engineering, Suwon (Korea, Republic of)

    2016-01-15

    The aim of our study was to determine the diagnostic value of a novel image analysis method called parametric response mapping (PRM) for prediction of intrahepatic recurrence of hepatocellular carcinoma (HCC) treated with conventional transcatheter arterial chemoembolization (TACE). This retrospective study was approved by the IRB. We recruited 55 HCC patients who achieved complete remission (CR) after TACE and received longitudinal multiphasic liver computed tomography (CT). The patients fell into two groups: the recurrent tumour group (n = 29) and the non-recurrent tumour group (n = 26). We applied the PRM analysis to see if this technique could distinguish between the two groups. The results of the PRM analysis were incorporated into a prediction algorithm. We retrospectively removed data from the last time point and attempted to predict the response to therapy of the removed data. The PRM analysis was able to distinguish between the non-recurrent and recurrent groups successfully. The prediction algorithm detected response to therapy with an area under the curve (AUC) of 0.76, while the manual approach had AUC 0.64. Adopting PRM analysis can potentially distinguish between recurrent and non-recurrent HCCs and allow for prediction of response to therapy after TACE. (orig.)

  14. Cellular unfolded protein response against viruses used in gene therapy

    Directory of Open Access Journals (Sweden)

    Dwaipayan eSen

    2014-05-01

    Full Text Available Viruses are excellent vehicles for gene therapy due to their natural ability to infect and deliver the cargo to specific tissues with high efficiency. Although such vectors are usually ‘gutted’ and are replication defective, they are subjected to clearance by the host cells by immune recognition and destruction. Unfolded protein response (UPR is a naturally evolved cyto-protective signaling pathway which is triggered due to endoplasmic reticulum (ER stress caused by accumulation of unfolded/misfolded proteins in its lumen. The UPR signaling consists of three signaling pathways, namely PKR-like ER kinase, activating transcription factor 6, and inositol-requiring protein-1. Once activated, UPR triggers the production of ER molecular chaperones and stress response proteins to help reduce the protein load within the ER. This occurs by degradation of the misfolded proteins and ensues in the arrest of protein translation machinery. If the burden of protein load in ER is beyond its processing capacity, UPR can activate pro-apoptotic pathways or autophagy leading to cell death. Viruses are naturally evolved in hijacking the host cellular translation machinery to generate a large amount of proteins. This phenomenon disrupts ER homeostasis and leads to ER stress. Alternatively, in the case of gutted vectors used in gene therapy, the excess load of recombinant vectors administered and encountered by the cell can trigger UPR. Thus, in the context of gene therapy, UPR becomes a major roadblock that can potentially trigger inflammatory responses against the vectors and reduce the efficiency of gene transfer.

  15. BRCA1 Mutation: A Predictive Marker for Radiation Therapy?

    Energy Technology Data Exchange (ETDEWEB)

    Kan, Charlene; Zhang, Junran, E-mail: Junran.zhang@case.edu

    2015-10-01

    DNA repair, in particular, DNA double-strand break (DSB) repair, is essential for the survival of both normal and cancer cells. An elaborate repair mechanism has been developed in cells to efficiently repair the damaged DNA. The pathways predominately involved in DSB repair are homologous recombination and classic nonhomologous end-joining, although the alternative NHEJ pathway, a third DSB repair pathway, could also be important in certain contexts. The protein of BRCA1 encoded by the tumor suppressor gene BRCA1 regulates all DSB repair pathways. Given that DSBs represent the most biologically significant lesions induced by ionizing radiation and that impaired DSB repair leads to radiation sensitivity, it has been expected that cancer patients with BRCA1 mutations should benefit from radiation therapy. However, the clinical data have been conflicting and inconclusive. We provide an overview about the current status of the data regarding BRCA1 deficiency and radiation therapy sensitivity in both experimental models and clinical investigations. In addition, we discuss a strategy to potentiate the effects of radiation therapy by poly(ADP-ribose) polymerase inhibitors, the pharmacologic drugs being investigated as monotherapy for the treatment of patients with BRCA1/2 mutations.

  16. Neoadjuvant palbociclib on ER+ breast cancer (N007): clinical response and EndoPredict value.

    Science.gov (United States)

    Chow, Louis Wc; Morita, Satoshi; Chow, Christopher Yc; Ng, Wai Kuen; Toi, Masakazu

    2017-11-20

    To test the efficacy of neoadjuvant palbociclib therapy and to evaluate its impact on cell cycle arrest and changes in EndoPredict (EP) scores before and after treatment. Postmenopausal women with histologically proven ER+ve, HER2-ve invasive breast cancer, 2cm or greater, were enrolled in an open-label, single arm study. Twenty eligible patients were given letrozole 2.5mg per day together with palbociclib 125mg per day for 3 out of 4 weeks in repeated cycles for 16 weeks (4 cycles) before surgery. The primary end-points were clinical response rates (cRR) and preoperative endocrine prognostic index (PEPI). The secondary end-points were pathologic response and gene expression testing with EP test on collected tumor samples. 17 patients showed a clinical response of 50% or more, including 8 complete response and 9 partial response. There was significant reduction in area (Ppalbociclib treatment. 6 patients with intermediate and three patients with high PEPI risk scores were found to have low EPclin scores. All patients with high PEPI relapse risk score had high EPclin score. Effective clinical response was demonstrated by neoadjuvant letrozole in combination with palbociclib. Compared with PEPI, EPclin might be a better parameter to estimate prognosis after neoadjuvant therapy.

  17. Electroconvulsive therapy in catatonic patients: Efficacy and predictors of response.

    Science.gov (United States)

    Luchini, Federica; Medda, Pierpaolo; Mariani, Michela Giorgi; Mauri, Mauro; Toni, Cristina; Perugi, Giulio

    2015-06-22

    Recent evidence favors the view of catatonia as an autonomous syndrome, frequently associated with mood disorders, but also observed in neurological, neurodevelopmental, physical and toxic conditions. From our systematic literature review, electroconvulsive therapy (ECT) results effective in all forms of catatonia, even after pharmacotherapy with benzodiazepines has failed. Response rate ranges from 80% to 100% and results superior to those of any other therapy in psychiatry. ECT should be considered first-line treatment in patients with malignant catatonia, neuroleptic malignant syndrome, delirious mania or severe catatonic excitement, and in general in all catatonic patients that are refractory or partially responsive to benzodiazepines. Early intervention with ECT is encouraged to avoid undue deterioration of the patient's medical condition. Little is known about the long-term treatment outcomes following administration of ECT for catatonia. The presence of a concomitant chronic neurologic disease or extrapyramidal deficit seems to be related to ECT non-response. On the contrary, the presence of acute, severe and psychotic mood disorder is associated with good response. Severe psychotic features in responders may be related with a prominent GABAergic mediated deficit in orbitofrontal cortex, whereas non-responders may be characterized by a prevalent dopaminergic mediated extrapyramidal deficit. These observations are consistent with the hypothesis that ECT is more effective in "top-down" variant of catatonia, in which the psychomotor syndrome may be sustained by a dysregulation of the orbitofrontal cortex, than in "bottom-up" variant, in which an extrapyramidal dysregulation may be prevalent. Future research should focus on ECT response in different subtype of catatonia and on efficacy of maintenance ECT in long-term prevention of recurrent catatonia. Further research on mechanism of action of ECT in catatonia may also contribute to the development of other

  18. Using adaptive model predictive control to customize maintenance therapy chemotherapeutic dosing for childhood acute lymphoblastic leukemia.

    Science.gov (United States)

    Noble, Sarah L; Sherer, Eric; Hannemann, Robert E; Ramkrishna, Doraiswami; Vik, Terry; Rundell, Ann E

    2010-06-07

    Acute lymphoblastic leukemia (ALL) is a common childhood cancer in which nearly one-quarter of patients experience a disease relapse. However, it has been shown that individualizing therapy for childhood ALL patients by adjusting doses based on the blood concentration of active drug metabolite could significantly improve treatment outcome. An adaptive model predictive control (MPC) strategy is presented in which maintenance therapy for childhood ALL is personalized using routine patient measurements of red blood cell mean corpuscular volume as a surrogate for the active drug metabolite concentration. A clinically relevant mathematical model is developed and used to describe the patient response to the chemotherapeutic drug 6-mercaptopurine, with some model parameters being patient-specific. During the course of treatment, the patient-specific parameters are adaptively identified using recurrent complete blood count measurements, which sufficiently constrain the patient parameter uncertainty to support customized adjustments of the drug dose. While this work represents only a first step toward a quantitative tool for clinical use, the simulated treatment results indicate that the proposed mathematical model and adaptive MPC approach could serve as valuable resources to the oncologist toward creating a personalized treatment strategy that is both safe and effective. Copyright (c) 2010 Elsevier Ltd. All rights reserved.

  19. Evaluating effects of normobaric oxygen therapy in acute stroke with MRI-based predictive models

    Directory of Open Access Journals (Sweden)

    Wu Ona

    2012-03-01

    Full Text Available Abstract Background Voxel-based algorithms using acute multiparametric-MRI data have been shown to accurately predict tissue outcome after stroke. We explored the potential of MRI-based predictive algorithms to objectively assess the effects of normobaric oxygen therapy (NBO, an investigational stroke treatment, using data from a pilot study of NBO in acute stroke. Methods The pilot study of NBO enrolled 11 patients randomized to NBO administered for 8 hours, and 8 Control patients who received room-air. Serial MRIs were obtained at admission, during gas therapy, post-therapy, and pre-discharge. Diffusion/perfusion MRI data acquired at admission (pre-therapy was used in generalized linear models to predict the risk of lesion growth at subsequent time points for both treatment scenarios: NBO or Control. Results Lesion volume sizes 'during NBO therapy' predicted by Control-models were significantly larger (P = 0.007 than those predicted by NBO models, suggesting that ischemic lesion growth is attenuated during NBO treatment. No significant difference was found between the predicted lesion volumes at later time-points. NBO-treated patients, despite showing larger lesion volumes on Control-models than NBO-models, tended to have reduced lesion growth. Conclusions This study shows that NBO has therapeutic potential in acute ischemic stroke, and demonstrates the feasibility of using MRI-based algorithms to evaluate novel treatments in early-phase clinical trials.

  20. Predictors of response to physical therapy intervention in patients with primary hip osteoarthritis.

    Science.gov (United States)

    Wright, Alexis A; Cook, Chad E; Flynn, Timothy W; Baxter, G David; Abbott, J Haxby

    2011-04-01

    Few studies have investigated or identified common clinical tests and measures as being associated with progression of hip osteoarthritis (OA); fewer still are longitudinal studies exploring prognostic variables associated with long-term outcome following physical therapy treatment. The purpose of this study was to determine a set of prognostic factors that maximize the accuracy of identifying patients with hip osteoarthritis (OA) likely to demonstrate a favorable response to physical therapy intervention. This was a prognostic study. Ninety-one patients with a clinical diagnosis of hip OA were analyzed to determine which clinical measures, when clustered together, were most predictive of a favorable response to physical therapy intervention. Responders were determined based on OMERACT-OARSI response criteria, which included percent and absolute changes in pain, function, and global rating of change over 1 year. These data served as the reference standard for determining the predictive validity of baseline clinical examination variables. Using multivariate regression analyses and calculations for sensitivity, specificity, and positive and negative likelihood ratios, a cluster was identified. Five baseline variables (unilateral hip pain, age of ≤58 years, pain of ≥6/10 on a numeric pain rating scale, 40-m self-paced walk test time of ≤25.9 seconds, and duration of symptoms of ≤1 year) were retained in the final model. Failure to exhibit a condition of 1 of the 5 predictor variables decreased the posttest probability of responding favorably to physical therapy intervention from 32% to physical therapy intervention from 32% to 65% (positive likelihood ratio=3.99, 95% confidence interval=2.66-4.48), and having 3 or more of 5 predictor variables increased the posttest probability of success to 99% or higher. A comparison with a control group that did not receive physical therapy further substantiated the cluster. The small sample size and the number of variables

  1. An erythroid differentiation signature predicts response to lenalidomide in myelodysplastic syndrome.

    Directory of Open Access Journals (Sweden)

    Benjamin L Ebert

    2008-02-01

    Full Text Available Lenalidomide is an effective new agent for the treatment of patients with myelodysplastic syndrome (MDS, an acquired hematopoietic disorder characterized by ineffective blood cell production and a predisposition to the development of leukemia. Patients with an interstitial deletion of Chromosome 5q have a high rate of response to lenalidomide, but most MDS patients lack this deletion. Approximately 25% of patients without 5q deletions also benefit from lenalidomide therapy, but response in these patients cannot be predicted by any currently available diagnostic assays. The aim of this study was to develop a method to predict lenalidomide response in order to avoid unnecessary toxicity in patients unlikely to benefit from treatment.Using gene expression profiling, we identified a molecular signature that predicts lenalidomide response. The signature was defined in a set of 16 pretreatment bone marrow aspirates from MDS patients without 5q deletions, and validated in an independent set of 26 samples. The response signature consisted of a cohesive set of erythroid-specific genes with decreased expression in responders, suggesting that a defect in erythroid differentiation underlies lenalidomide response. Consistent with this observation, treatment with lenalidomide promoted erythroid differentiation of primary hematopoietic progenitor cells grown in vitro.These studies indicate that lenalidomide-responsive patients have a defect in erythroid differentiation, and suggest a strategy for a clinical test to predict patients most likely to respond to the drug. The experiments further suggest that the efficacy of lenalidomide, whose mechanism of action in MDS is unknown, may be due to its ability to induce erythroid differentiation.

  2. Remodeling of Tumor Stroma and Response to Therapy

    Energy Technology Data Exchange (ETDEWEB)

    Johansson, Anna; Ganss, Ruth, E-mail: ganss@waimr.uwa.edu.au [Western Australian Institute for Medical Research, Centre for Medical Research, University of Western Australia, Perth 6000 (Australia)

    2012-03-27

    Solid tumors are intrinsically resistant to therapy. Cancer progression occurs when tumor cells orchestrate responses from diverse stromal cell types such as blood vessels and their support cells, inflammatory cells, and fibroblasts; these cells collectively form the tumor microenvironment and provide direct support for tumor growth, but also evasion from cytotoxic, immune and radiation therapies. An indirect result of abnormal and leaky blood vessels in solid tumors is high interstitial fluid pressure, which reduces drug penetration, but also creates a hypoxic environment that further augments tumor cell growth and metastatic spread. Importantly however, studies during the last decade have shown that the tumor stroma, including the vasculature, can be modulated, or re-educated, to allow better delivery of chemotherapeutic drugs or enhance the efficiency of active immune therapy. Such remodeling of the tumor stroma using genetic, pharmacological and other therapeutic approaches not only enhances selective access into tumors but also reduces toxic side effects. This review focuses on recent novel concepts to modulate tumor stroma and thus locally increase therapeutic efficacy.

  3. The Role of Occupational Voice Demand and Patient-Rated Impairment in Predicting Voice Therapy Adherence.

    Science.gov (United States)

    Ebersole, Barbara; Soni, Resha S; Moran, Kathleen; Lango, Miriam; Devarajan, Karthik; Jamal, Nausheen

    2017-07-11

    Examine the relationship among the severity of patient-perceived voice impairment, perceptual dysphonia severity, occupational voice demand, and voice therapy adherence. Identify clinical predictors of increased risk for therapy nonadherence. A retrospective cohort study of patients presenting with a chief complaint of persistent dysphonia at an interdisciplinary voice center was done. The Voice Handicap Index-10 (VHI-10) and the Voice-Related Quality of Life (V-RQOL) survey scores, clinician rating of dysphonia severity using the Grade score from the Grade, Roughness Breathiness, Asthenia, and Strain scale, occupational voice demand, and patient demographics were tested for associations with therapy adherence, defined as completion of the treatment plan. Classification and Regression Tree (CART) analysis was performed to establish thresholds for nonadherence risk. Of 166 patients evaluated, 111 were recommended for voice therapy. The therapy nonadherence rate was 56%. Occupational voice demand category, VHI-10, and V-RQOL scores were the only factors significantly correlated with therapy adherence (P occupational voice demand are significantly more likely to be nonadherent with therapy than those with high occupational voice demand (P 40 is a significant cutoff point for predicting therapy nonadherence (P Occupational voice demand and patient perception of impairment are significantly and independently correlated with therapy adherence. A VHI-10 score of ≤9 or a V-RQOL score of >40 is a significant cutoff point for predicting nonadherence risk. Copyright © 2017 The Voice Foundation. Published by Elsevier Inc. All rights reserved.

  4. PET/CT for therapy response assessment in lymphoma

    DEFF Research Database (Denmark)

    Hutchings, Martin; Barrington, Sally F

    2009-01-01

    PET with (18)F-FDG is a standard staging procedure for most lymphoma subtypes. Performed during and after therapy for Hodgkin lymphoma (HL) and aggressive non-Hodgkin lymphoma (NHL), (18)F-FDG PET results have a high prognostic value and correlate with survival. (18)F-FDG PET has been incorporated...... into revised response criteria for aggressive lymphomas, and several ongoing trials are under way to investigate the value of treatment adaptation based on early (18)F-FDG PET results for HL and aggressive NHL. There is little evidence to support the use of (18)F-FDG PET for monitoring of the treatment...... of indolent lymphomas and for routine use in the surveillance setting. So that trial results can be compared and translated easily into clinical practice, uniform and evidence-based guidelines for the interpretation and reporting of response monitoring scans are warranted. Because it is still not proven...

  5. Photodynamic therapy induces an immune response against a bacterial pathogen.

    Science.gov (United States)

    Huang, Ying-Ying; Tanaka, Masamitsu; Vecchio, Daniela; Garcia-Diaz, Maria; Chang, Julie; Morimoto, Yuji; Hamblin, Michael R

    2012-07-01

    Photodynamic therapy (PDT) employs the triple combination of photosensitizers, visible light and ambient oxygen. When PDT is used for cancer, it has been observed that both arms of the host immune system (innate and adaptive) are activated. When PDT is used for infectious disease, however, it has been assumed that the direct antimicrobial PDT effect dominates. Murine arthritis caused by methicillin-resistant Staphylococcus aureus in the knee failed to respond to PDT with intravenously injected Photofrin(®). PDT with intra-articular Photofrin produced a biphasic dose response that killed bacteria without destroying host neutrophils. Methylene blue was the optimum photosensitizer to kill bacteria while preserving neutrophils. We used bioluminescence imaging to noninvasively monitor murine bacterial arthritis and found that PDT with intra-articular methylene blue was not only effective, but when used before infection, could protect the mice against a subsequent bacterial challenge. The data emphasize the importance of considering the host immune response in PDT for infectious disease.

  6. Metformin: A Novel Biological Modifier of Tumor Response to Radiation Therapy

    Energy Technology Data Exchange (ETDEWEB)

    Koritzinsky, Marianne, E-mail: mkoritzi@uhnresearch.ca

    2015-10-01

    Over the last decade, evidence has emerged to support a role for the antidiabetic drug metformin in the prevention and treatment of cancer. In particular, recent studies demonstrate that metformin enhances tumor response to radiation in experimental models, and retrospective analyses have shown that diabetic cancer patients treated with radiation therapy have improved outcomes if they take metformin to control their diabetes. Metformin may therefore be of utility for nondiabetic cancer patients treated with radiation therapy. The purpose of this review is to examine the data pertaining to an interaction between metformin and radiation, highlighting the essential steps needed to advance our current knowledge. There is also a focus on key biomarkers that should accompany prospective clinical trials in which metformin is being examined as a modifying agent with radiation therapy. Existing evidence supports that the mechanism underlying the ability of metformin to enhance radiation response is multifaceted, and includes direct radiosensitization as well as a reduction in tumor stem cell fraction, proliferation, and tumor hypoxia. Interestingly, metformin may enhance radiation response specifically in certain genetic backgrounds, such as in cells with loss of the tumor suppressors p53 and LKB1, giving rise to a therapeutic ratio and potential predictive biomarkers.

  7. Predicting aquifer response time for application in catchment modeling.

    Science.gov (United States)

    Walker, Glen R; Gilfedder, Mat; Dawes, Warrick R; Rassam, David W

    2015-01-01

    It is well established that changes in catchment land use can lead to significant impacts on water resources. Where land-use changes increase evapotranspiration there is a resultant decrease in groundwater recharge, which in turn decreases groundwater discharge to streams. The response time of changes in groundwater discharge to a change in recharge is a key aspect of predicting impacts of land-use change on catchment water yield. Predicting these impacts across the large catchments relevant to water resource planning can require the estimation of groundwater response times from hundreds of aquifers. At this scale, detailed site-specific measured data are often absent, and available spatial data are limited. While numerical models can be applied, there is little advantage if there are no detailed data to parameterize them. Simple analytical methods are useful in this situation, as they allow the variability in groundwater response to be incorporated into catchment hydrological models, with minimal modeling overhead. This paper describes an analytical model which has been developed to capture some of the features of real, sloping aquifer systems. The derived groundwater response timescale can be used to parameterize a groundwater discharge function, allowing groundwater response to be predicted in relation to different broad catchment characteristics at a level of complexity which matches the available data. The results from the analytical model are compared to published field data and numerical model results, and provide an approach with broad application to inform water resource planning in other large, data-scarce catchments. © 2014, CommonWealth of Australia. Groundwater © 2014, National Ground Water Association.

  8. The potential use of expression profiling: implications for predicting treatment response in rheumatoid arthritis.

    Science.gov (United States)

    Smith, Samantha Louise; Plant, Darren; Eyre, Stephen; Barton, Anne

    2013-07-01

    Whole genome expression profiling, or transcriptomics, is a high throughput technology with the potential for major impacts in both clinical settings and drug discovery and diagnostics. In particular, there is much interest in this technique as a mechanism for predicting treatment response. Gene expression profiling entails the quantitative measurement of messenger RNA levels for thousands of genes simultaneously with the inherent possibility of identifying biomarkers of response to a particular therapy or by singling out those at risk of serious adverse events. This technology should contribute to the era of stratified medicine, in which patient specific populations are matched to potentially beneficial drugs via clinical tests. Indeed, in the oncology field, gene expression testing is already recommended to allow rational use of therapies to treat breast cancer. However, there are still many issues surrounding the use of the various testing platforms available and the statistical analysis associated with the interpretation of results generated. This review will discuss the implications this promising technology has in predicting treatment response and outline the various advantages and pitfalls associated with its use.

  9. Predicting adherence to antiretroviral therapy among pregnant women in Guyana: Utility of the Health Belief Model.

    Science.gov (United States)

    Vitalis, Deborah

    2017-07-01

    Barriers to antiretroviral therapy (ART) adherence among pregnant women are varied and complex. This study explored the constructs of a theoretical model, the Health Belief Model (HBM) to understand and predict ART adherence among pregnant women in Guyana. A cross-sectional study surveyed 108 pregnant women attending 11 primary care clinics. ART adherence ranging from the past weekend to three months was assessed through self-reports, and health beliefs with the Adherence Determinants Questionnaire (ADQ). Constructs with sufficient variation in responses were tested for association with the level of adherence using Spearman's rank correlation coefficient and test. Sixty-seven per cent (72) of the women reported being always adherent. Although there was positive endorsement of ART treatment and adherence, the HBM did not help in understanding or predicting ART adherence in this population. Only one item from the perceived susceptibility construct was significantly associated (p = 0.009) with adherence. Interventions are warranted to address ART adherence in this population, as 19% of the women were recently non-adherent. Although the ADQ did not contribute to a deeper understanding or provide insight into pathways that can be targeted for intervention, theoretical models can play a key role in identifying these pathways.

  10. Development of agent based model for predicting emergency response time

    Directory of Open Access Journals (Sweden)

    Mainak Bandyopadhyay

    2016-09-01

    Full Text Available Determining the time to reach any incident location by an emergency service is a very important aspect for emergency management. In most of the developing countries road network is considered as a main infrastructure for transporting emergency services. Therefore in order to predict the response time consideration must be given to the characteristics of road segments and driving behaviour of emergency vehicle drivers. In this paper real time driving data by Fire emergency service of Allahabad city is collected using GPS logger HOLUX M1000C. The spatial trajectories collected from GPS logger are analysed in GIS along with road network, population density and landuse data to determine the driver's route deciding behaviour. Based on the integrated analysis the Fire Emergency Vehicle Agent is designed. The Agent based model is simulated to determine the response time which is subsequently compared with the real response time.

  11. Prediction of outcome in internet-delivered cognitive behaviour therapy for paediatric obsessive-compulsive disorder: A machine learning approach.

    Science.gov (United States)

    Lenhard, Fabian; Sauer, Sebastian; Andersson, Erik; Månsson, Kristoffer Nt; Mataix-Cols, David; Rück, Christian; Serlachius, Eva

    2017-07-28

    There are no consistent predictors of treatment outcome in paediatric obsessive-compulsive disorder (OCD). One reason for this might be the use of suboptimal statistical methodology. Machine learning is an approach to efficiently analyse complex data. Machine learning has been widely used within other fields, but has rarely been tested in the prediction of paediatric mental health treatment outcomes. To test four different machine learning methods in the prediction of treatment response in a sample of paediatric OCD patients who had received Internet-delivered cognitive behaviour therapy (ICBT). Participants were 61 adolescents (12-17 years) who enrolled in a randomized controlled trial and received ICBT. All clinical baseline variables were used to predict strictly defined treatment response status three months after ICBT. Four machine learning algorithms were implemented. For comparison, we also employed a traditional logistic regression approach. Multivariate logistic regression could not detect any significant predictors. In contrast, all four machine learning algorithms performed well in the prediction of treatment response, with 75 to 83% accuracy. The results suggest that machine learning algorithms can successfully be applied to predict paediatric OCD treatment outcome. Validation studies and studies in other disorders are warranted. Copyright © 2017 John Wiley & Sons, Ltd.

  12. Predicting Response to Neoadjuvant Chemotherapy with PET Imaging Using Convolutional Neural Networks.

    Directory of Open Access Journals (Sweden)

    Petros-Pavlos Ypsilantis

    Full Text Available Imaging of cancer with 18F-fluorodeoxyglucose positron emission tomography (18F-FDG PET has become a standard component of diagnosis and staging in oncology, and is becoming more important as a quantitative monitor of individual response to therapy. In this article we investigate the challenging problem of predicting a patient's response to neoadjuvant chemotherapy from a single 18F-FDG PET scan taken prior to treatment. We take a "radiomics" approach whereby a large amount of quantitative features is automatically extracted from pretherapy PET images in order to build a comprehensive quantification of the tumor phenotype. While the dominant methodology relies on hand-crafted texture features, we explore the potential of automatically learning low- to high-level features directly from PET scans. We report on a study that compares the performance of two competing radiomics strategies: an approach based on state-of-the-art statistical classifiers using over 100 quantitative imaging descriptors, including texture features as well as standardized uptake values, and a convolutional neural network, 3S-CNN, trained directly from PET scans by taking sets of adjacent intra-tumor slices. Our experimental results, based on a sample of 107 patients with esophageal cancer, provide initial evidence that convolutional neural networks have the potential to extract PET imaging representations that are highly predictive of response to therapy. On this dataset, 3S-CNN achieves an average 80.7% sensitivity and 81.6% specificity in predicting non-responders, and outperforms other competing predictive models.

  13. Myopodin methylation is a prognostic biomarker and predicts antiangiogenic response in advanced kidney cancer.

    Science.gov (United States)

    Pompas-Veganzones, N; Sandonis, V; Perez-Lanzac, Alberto; Beltran, M; Beardo, P; Juárez, A; Vazquez, F; Cozar, J M; Alvarez-Ossorio, J L; Sanchez-Carbayo, Marta

    2016-10-01

    Myopodin is a cytoskeleton protein that shuttles to the nucleus depending on the cellular differentiation and stress. It has shown tumor suppressor functions. Myopodin methylation status was useful for staging bladder and colon tumors and predicting clinical outcome. To our knowledge, myopodin has not been tested in kidney cancer to date. The purpose of this study was to evaluate whether myopodin methylation status could be clinically useful in renal cancer (1) as a prognostic biomarker and 2) as a predictive factor of response to antiangiogenic therapy in patients with metastatic disease. Methylation-specific polymerase chain reactions (MS-PCR) were used to evaluate myopodin methylation in 88 kidney tumors. These belonged to patients with localized disease and no evidence of disease during follow-up (n = 25) (group 1), and 63 patients under antiangiogenic therapy (sunitinib, sorafenib, pazopanib, and temsirolimus), from which group 2 had non-metastatic disease at diagnosis (n = 32), and group 3 showed metastatic disease at diagnosis (n = 31). Univariate and multivariate Cox analyses were utilized to assess outcome and response to antiangiogenic agents taking progression, disease-specific survival, and overall survival as clinical endpoints. Myopodin was methylated in 50 out of the 88 kidney tumors (56.8 %). Among the 88 cases analyzed, 10 of them recurred (11.4 %), 51 progressed (57.9 %), and 40 died of disease (45.4 %). Myopodin methylation status correlated to MSKCC Risk score (p = 0.050) and the presence of distant metastasis (p = 0.039). Taking all patients, an unmethylated myopodin identified patients with shorter progression-free survival, disease-specific survival, and overall survival. Using also in univariate and multivariate models, an unmethylated myopodin predicted response to antiangiogenic therapy (groups 2 and 3) using progression-free survival, disease-specific, and overall survival as clinical endpoints. Myopodin was revealed

  14. Clinical predictive factors of sildenafil response: a penile hemodynamic study.

    Science.gov (United States)

    Elhanbly, S M; Elkholy, A A-M; Alghobary, M; Abou Al-Ghar, M

    2015-03-01

    Phosphodiestrase-5 inhibitors are an important line of treatment for erectile dysfunction (ED). To detect the clinical and hemodynamic predictors of sildenafil response, we conducted this study on 124 Egyptian men with ED. All patients were evaluated by thorough history and clinical assessment with measurement of the abridged international index of erectile function-5 (IIEF-5) score. All patients were then subjected to intracavernosal injection (ICI) of trimix and pharmaco-penile duplex ultrasonography (PPDU). Patients were then classified into sildenafil responders and non-responders after six consecutive doses of 100 mg sildenafil. On doing the binary logistic stepwise regression analysis, only ED duration, IIEF-5 score, and response to ICI were the significant independent predictors of sildenafil response. These three parameters together correctly predicted the sildenafil response by 81.5% (p value <0.001). With the receiver operator characteristic curve analysis, the cut-off value of ED duration was 2.5 years and it was 14 for the IIEF-5 score. These findings indicate that ED duration, the IIEF-5 score and response to ICI are more significant predictors of sildenafil response than the more expensive and time-consuming PPDU testing. © 2015 American Society of Andrology and European Academy of Andrology.

  15. Neutrophil-to-Lymphocyte Ratio for Predicting Loss of Response to Infliximab in Ulcerative Colitis.

    Science.gov (United States)

    Nishida, Yu; Hosomi, Shuhei; Yamagami, Hirokazu; Yukawa, Tomomi; Otani, Koji; Nagami, Yasuaki; Tanaka, Fumio; Taira, Koichi; Kamata, Noriko; Tanigawa, Tetsuya; Shiba, Masatsugu; Watanabe, Kenji; Watanabe, Toshio; Tominaga, Kazunari; Fujiwara, Yasuhiro

    2017-01-01

    Neutrophil-to-lymphocyte ratio (NLR) has been used to determine the outcome in malignancies and coronary heart disease. Some reports considered the value of NLR as a predictor of response to infliximab in patients with Crohn's disease or rheumatoid arthritis; however, no similar studies have been reported for ulcerative colitis (UC). This study aimed to evaluate the clinical significance of the baseline NLR in patients with UC treated by infliximab. Patients with moderate-to-severe active UC who received the first infliximab infusion in our hospital between 2010 and 2015, who showed clinical response during the induction period, were retrospectively evaluated for long-term outcomes and risk factors for loss of response (LOR) during infliximab maintenance therapy. Baseline inflammatory markers including NLR were measured within one week before the initiation of infliximab. Fifty-nine patients with moderate-to-severe active UC started treatment with infliximab and 37 patients (62.7%) experienced clinical response after induction therapy. Fourteen of 37 patients on maintenance therapy lost the response during follow-up. Baseline NLR of patients with LOR was significantly higher than in patients with sustained response. The NLR cut-off value of 4.488 was predictive of LOR, using receiver operating characteristic analysis (sensitivity: 78.6%, specificity: 78.3%). A univariate analysis revealed a significant relationship between relapse-free survival and the NLR (P = 0.018). Multivariate analysis indicated the NLR as an independent prognostic factor for LOR (hazard ratio = 3.86, 95% confidence interval: 1.20-12.4, P = 0.023). Baseline NLR is a useful prognostic marker in patients with moderate-to-severe active UC treated with infliximab, and may contribute to appropriate use of infliximab.

  16. Can We Predict Individual Combined Benefit and Harm of Therapy? Warfarin Therapy for Atrial Fibrillation as a Test Case.

    Directory of Open Access Journals (Sweden)

    Guowei Li

    Full Text Available To construct and validate a prediction model for individual combined benefit and harm outcomes (stroke with no major bleeding, major bleeding with no stroke, neither event, or both in patients with atrial fibrillation (AF with and without warfarin therapy.Using the Kaiser Permanente Colorado databases, we included patients newly diagnosed with AF between January 1, 2005 and December 31, 2012 for model construction and validation. The primary outcome was a prediction model of composite of stroke or major bleeding using polytomous logistic regression (PLR modelling. The secondary outcome was a prediction model of all-cause mortality using the Cox regression modelling.We included 9074 patients with 4537 and 4537 warfarin users and non-users, respectively. In the derivation cohort (n = 4632, there were 136 strokes (2.94%, 280 major bleedings (6.04% and 1194 deaths (25.78% occurred. In the prediction models, warfarin use was not significantly associated with risk of stroke, but increased the risk of major bleeding and decreased the risk of death. Both the PLR and Cox models were robust, internally and externally validated, and with acceptable model performances.In this study, we introduce a new methodology for predicting individual combined benefit and harm outcomes associated with warfarin therapy for patients with AF. Should this approach be validated in other patient populations, it has potential advantages over existing risk stratification approaches as a patient-physician aid for shared decision-making.

  17. Pretreatment Growth Rate Predicts Radiation Response in Vestibular Schwannomas

    Energy Technology Data Exchange (ETDEWEB)

    Niu, Nina N. [Department of Radiation Oncology, Harvard Medical School, Massachusetts General Hospital, Boston, Massachusetts (United States); Harvard Medical School, Department of Medicine, Brigham and Women' s Hospital, Boston, Massachusetts (United States); Niemierko, Andrzej [Department of Radiation Oncology, Harvard Medical School, Massachusetts General Hospital, Boston, Massachusetts (United States); Larvie, Mykol [Harvard Medical School, Department of Radiology, Massachusetts General Hospital, Boston, Massachusetts (United States); Curtin, Hugh [Harvard Medical School, Department of Radiology, Massachusetts Eye and Ear Infirmary, Boston, Massachusetts (United States); Loeffler, Jay S. [Department of Radiation Oncology, Harvard Medical School, Massachusetts General Hospital, Boston, Massachusetts (United States); McKenna, Michael J. [Harvard Medical School, Department of Otolaryngology, Massachusetts Eye and Ear Infirmary, Boston, Massachusetts (United States); Shih, Helen A., E-mail: hshih@partners.org [Department of Radiation Oncology, Harvard Medical School, Massachusetts General Hospital, Boston, Massachusetts (United States)

    2014-05-01

    Purpose: Vestibular schwannomas (VS) are often followed without initial therapeutic intervention because many tumors do not grow and radiation therapy is associated with potential adverse effects. In an effort to determine whether maximizing initial surveillance predicts for later treatment response, the predictive value of preirradiation growth rate of VS on response to radiation therapy was assessed. Methods and Materials: Sixty-four patients with 65 VS were treated with single-fraction stereotactic radiation surgery or fractionated stereotactic radiation therapy. Pre- and postirradiation linear expansion rates were estimated using volumetric measurements on sequential magnetic resonance images (MRIs). In addition, postirradiation tumor volume change was classified as demonstrating shrinkage (ratio of volume on last follow-up MRI to MRI immediately preceding irradiation <80%), stability (ratio 80%-120%), or expansion (ratio >120%). The median pre- and postirradiation follow-up was 20.0 and 27.5 months, respectively. Seven tumors from neurofibromatosis type 2 (NF2) patients were excluded from statistical analyses. Results: In the 58 non-NF2 patients, there was a trend of correlation between pre- and postirradiation volume change rates (slope on linear regression, 0.29; P=.06). Tumors demonstrating postirradiation expansion had a median preirradiation growth rate of 89%/year, and those without postirradiation expansion had a median preirradiation growth rate of 41%/year (P=.02). As the preirradiation growth rate increased, the probability of postirradiation expansion also increased. Overall, 24.1% of tumors were stable, 53.4% experienced shrinkage, and 22.5% experienced expansion. Predictors of no postirradiation tumor expansion included no prior surgery (P=.01) and slower tumor growth rate (P=.02). The control of tumors in NF2 patients was only 43%. Conclusions: Radiation therapy is an effective treatment for VS, but tumors that grow quickly preirradiation may be

  18. Predicting the effect of cognitive therapy for depression: a study of unique and common factors.

    Science.gov (United States)

    Castonguay, L G; Goldfried, M R; Wiser, S; Raue, P J; Hayes, A M

    1996-06-01

    The ability of several process variables to predict therapy outcome was tested with 30 depressed clients who received cognitive therapy with or without medication. Two types of process variables were studied: 1 variable that is unique to cognitive therapy and 2 variables that this approach is assumed to share with other forms of treatment. The client's improvement was found to be predicted by the 2 common factors measured: the therapeutic alliance and the client's emotional involvement (experiencing). The results also indicated, however, that a unique aspect of cognitive therapy (i.e., therapist's focus on the impact of distorted cognitions on depressive symptoms) correlated negatively with outcome at the end of treatment. Descriptive analyses that were conducted to understand this negative correlation suggest that therapists sometimes increased their adherence to cognitive rationales and techniques to correct problems in the therapeutic alliance. Such increased focus, however, seems to worsen alliance strains, thereby interfering with therapeutic change.

  19. Use of Germline Polymorphisms in Predicting Concurrent Chemoradiotherapy Response in Esophageal Cancer

    Energy Technology Data Exchange (ETDEWEB)

    Chen, Pei-Chun [Department of Statistics and Informatics Science, Providence University, Taiwan (China); Chen, Yen-Ching [Institute of Epidemiology Preventive Medicine, College of Public Health, National Taiwan University, Taiwan (China); Research Center for Gene, Environment, and Human Health, College of Public Health, National Taiwan University, Taiwan (China); Department of Public Health, Institute of Epidemiology, National Taiwan University, Taiwan (China); Lai, Liang-Chuan [Graduate Institute of Physiology, National Taiwan University, Taiwan (China); Tsai, Mong-Hsun [Institute of Biotechnology, National Taiwan University, Taiwan (China); Chen, Shin-Kuang [National Clinical Trial and Research Center, National Taiwan University Hospital, Taiwan (China); Yang, Pei-Wen; Lee, Yung-Chie [Department of Surgery, National Taiwan University Hospital, Taiwan (China); Hsiao, Chuhsing K. [Research Center for Gene, Environment, and Human Health, College of Public Health, National Taiwan University, Taiwan (China); Department of Public Health, Institute of Epidemiology, National Taiwan University, Taiwan (China); Bioinformatics and Biostatistics Core, Research Center for Medical Excellence, National Taiwan University, Taiwan (China); Lee, Jang-Ming, E-mail: jangming@ntuh.gov.tw [Department of Surgery, National Taiwan University Hospital, Taiwan (China); Chuang, Eric Y., E-mail: chuangey@ntu.edu.tw [National Clinical Trial and Research Center, National Taiwan University Hospital, Taiwan (China); Bioinformatics and Biostatistics Core, Research Center for Medical Excellence, National Taiwan University, Taiwan (China); Graduate Institute of Biomedical Electronics and Bioinformatics, National Taiwan University, Taiwan (China)

    2012-04-01

    Purpose: To identify germline polymorphisms to predict concurrent chemoradiation therapy (CCRT) response in esophageal cancer patients. Materials and Methods: A total of 139 esophageal cancer patients treated with CCRT (cisplatin-based chemotherapy combined with 40 Gy of irradiation) and subsequent esophagectomy were recruited at the National Taiwan University Hospital between 1997 and 2008. After excluding confounding factors (i.e., females and patients aged {>=}70 years), 116 patients were enrolled to identify single nucleotide polymorphisms (SNPs) associated with specific CCRT responses. Genotyping arrays and mass spectrometry were used sequentially to determine germline polymorphisms from blood samples. These polymorphisms remain stable throughout disease progression, unlike somatic mutations from tumor tissues. Two-stage design and additive genetic models were adopted in this study. Results: From the 26 SNPs identified in the first stage, 2 SNPs were found to be significantly associated with CCRT response in the second stage. Single nucleotide polymorphism rs16863886, located between SGPP2 and FARSB on chromosome 2q36.1, was significantly associated with a 3.93-fold increase in pathologic complete response to CCRT (95% confidence interval 1.62-10.30) under additive models. Single nucleotide polymorphism rs4954256, located in ZRANB3 on chromosome 2q21.3, was associated with a 3.93-fold increase in pathologic complete response to CCRT (95% confidence interval 1.57-10.87). The predictive accuracy for CCRT response was 71.59% with these two SNPs combined. Conclusions: This is the first study to identify germline polymorphisms with a high accuracy for predicting CCRT response in the treatment of esophageal cancer.

  20. Can the success of structured therapy for giggle incontinence be predicted?

    Directory of Open Access Journals (Sweden)

    Onur Telli

    2016-04-01

    Full Text Available ABSTRACT Introduction: To evaluate possible factors that can guide the clinician to predict potential cases refractoriness to medical treatment for giggle incontinence (GI and to examine the effectiveness of different treatment modalities. Material and methods: The data of 48 children referred to pediatric urology outpatient clinic between 2000 and 2013 diagnosed as GI were reviewed. Mean age, follow-up, GI frequency, associated symptoms, medical and family history were noted. Incontinence frequency differed between several per day to less than once weekly. Children were evaluated with uroflowmetry-electromyography and post-void residual urine. Clinical success was characterized as a full or partial response, or nonresponse as defined by the International Children's Continence Society. Univariate analysis was used to find potential factors including age, sex, familial history, GI frequency, treatment modality and dysfunctional voiding to predict children who would possibly not respond to treatment. Results: Mean age of the patients was 8.4 years (range 5 to 16. Mean follow-up time and mean duration of asymptomatic period were noted as 6.7±1.4 years and 14.2±2.3 months respectively. While 12 patients were treated with only behavioral urotherapy (Group-1, 11 patients were treated with alpha-adrenergic blockers and behavioral urotherapy (Group-2 and 18 patients with methylphenidate and behavioral urotherapy (Group-3. Giggle incontinence was refractory to eight children in-group 1; six children in-group 2 and eight children in-group 3. Daily GI frequency and dysfunctional voiding diagnosed on uroflowmetry-EMG were found as outstanding predictive factors for resistance to treatment modalities. Conclusions: A variety of therapies for GI have more than 50% failure rate and a standard treatment for GI has not been established. The use of medications to treat these patients would not be recommended, as they appear to add no benefit to symptoms and may

  1. Predictive factors for response to Lamivudine in chronic hepatitis B

    Directory of Open Access Journals (Sweden)

    SILVA Luiz Caetano da

    2000-01-01

    Full Text Available BACKGROUND: Lamivudine has been shown to be an efficient drug for chronic hepatitis B (CHB treatment. AIM: To investigate predictive factors of response, using a quantitative method with high sensitivity. METHODS: We carried out a prospective trial of lamivudine in 35 patients with CHB and evidence for viral replication, regardless to their HBeAg status. Lamivudine was given for 12 months at 300 mg daily and 150 mg thereafter. Response was considered when DNA was undetectable by PCR after 6 months of treatment. Viral replication was monitored by end-point dilution PCR. Mutation associated with resistance to lamivudine was detected by DNA sequencing in non-responder patients. RESULTS: Response was observed in 23/35 patients (65.7% but only in 5/15 (33.3% HBeAg positive patients. Only three pre-treatment variables were associated to low response: HBeAg (p = 0.006, high viral load (DNA-VHB > 3 x 10(6 copies/ml (p = 0.004 and liver HBcAg (p = 0.0028. YMDD mutations were detected in 7/11 non-responder patients. CONCLUSIONS: HBeAg positive patients with high viral load show a high risk for developing drug resistance. On the other hand, HBeAg negative patients show a good response to lamivudine even with high viremia.

  2. Circulating SCCA-IgM complex is a useful biomarker to predict the outcome of therapy in hepatocellular carcinoma patients.

    Science.gov (United States)

    Guarino, Maria; Di Costanzo, Giovan G; Gallotta, Andrea; Tortora, Raffaella; Paneghetti, Laura; Auriemma, Francesco; Tuccillo, Concetta; Fassina, Giorgio; Caporaso, Nicola; Morisco, Filomena

    2017-10-01

    Hepatocellular carcinoma (HCC) develops in about 3-4% of cirrhotic patients every year. The squamous cell carcinoma antigen (SCCA) has been found elevated in liver cancer specimens by immunohistochemistry, and detected in complex with IgM (SCCA-IgM) in the serum of patients with HCC. The aim of this study was to evaluate the ability of serological SCCA-IgM levels to predict the efficacy of HCC therapy. From April 2012 to April 2014, 131 patients with a new diagnosis of HCC were enrolled. The HCC diagnosis was made according to the EASL guidelines. The patients were staged and treated according to the BCLC Staging System: BCLC stages A and B were treated with locoregional therapy, and BCLC stage C was treated with Sorafenib. Response to therapy was evaluated according to the mRECIST criteria. Serum SCCA-IgM levels were determined by a commercially available ELISA kit at basal time (T0) and after one month of treatment (T1). At baseline and one month into therapy, SCCA-IgM levels were significantly lower (p value SCCA-IgM level [25th + 75th percentile] at T0:115.1 AU/mL [50.0 + 174.4] vs. 149.1 AU/mL [111.3 + 198.8]; median SCCA-IgM level [25th + 75th percentile] at T1: 113.4 AU/mL [50.0 + 194.2] vs. 170.6 AU/mL [111.7 + 344.2]). Our study suggests that the SCCA-IgM determination could be helpful in predicting the response to therapy in patients with HCC.

  3. Oncolytic VSV Primes Differential Responses to Immuno-oncology Therapy.

    Science.gov (United States)

    Durham, Nicholas M; Mulgrew, Kathy; McGlinchey, Kelly; Monks, Noel R; Ji, Hong; Herbst, Ronald; Suzich, JoAnn; Hammond, Scott A; Kelly, Elizabeth J

    2017-08-02

    Vesicular stomatitis virus encoding the IFNβ transgene (VSV-IFNβ) is a mediator of potent oncolytic activity and is undergoing clinical evaluation for the treatment of solid tumors. Emerging preclinical and clinical data suggest treatment of tumors with oncolytic viruses may sensitize tumors to checkpoint inhibitors and increase the anti-tumor immune response. New generations of immuno-oncology molecules including T cell agonists are entering clinical development and could be hypothesized to enhance the activity of oncolytic viruses, including VSV-IFNβ. Here, we show that VSV-IFNβ exhibits multiple mechanisms of action, including direct cell killing, stimulation of an innate immune response, recruitment of CD8 T cells, and depletion of T regulatory cells. Moreover, VSV-IFNβ promotes the establishment of a CD8 T cell response to endogenous tumor antigens. Our data demonstrate a significant enhancement of anti-tumor function for VSV-IFNβ when combined with checkpoint inhibitors, but not OX40 agonists. While the addition of checkpoint inhibitors to VSV-IFNβ generated robust tumor growth inhibition, it resulted in no increase in viral replication, transgene expression, or immunophenotypic changes beyond treatment with VSV-IFNβ alone. We hypothesize that tumor-specific T cells generated by VSV-IFNβ retain activity due to a lack of immune exhaustion when checkpoint inhibitors were used. Copyright © 2017 The American Society of Gene and Cell Therapy. Published by Elsevier Inc. All rights reserved.

  4. Utilizing pre-therapy clinical schema and initial CT changes to predict progression-free survival in patients with metastatic renal cell carcinoma on VEGF-targeted therapy: a preliminary analysis.

    Science.gov (United States)

    Smith, Andrew D; Shah, Shetal N; Rini, Brian I; Lieber, Michael L; Remer, Erick M

    2013-10-01

    Because of varying treatment effectiveness with vascular endothelial growth factor (VEGF)-targeted therapy in patients with metastatic renal cell carcinoma (RCC), the association of prognostic pre-therapy clinical schema, initial post-therapy computed tomography (CT) findings, and combination thereof in predicting progression-free survival (PFS) was investigated. A predictive biomarker that combines clinical risk factors and CT imaging features associated with initial response to therapy would be useful in stratifying patients into risk groups to guide therapy, in designing and interpreting results of clinical trials, in planning risk-directed therapy, and in patient counseling. Early identification of poor responders using an imaging biomarker may reduce drug-related toxicity and cost and allow for a therapeutic intervention before disease burden significantly advances. For this institutional review board-approved HIPAA-compliant retrospective study, baseline data for 82 patients with metastatic RCC treated with sunitinib or sorafenib was obtained for risk stratification by Memorial Sloan Kettering Cancer Center (MSKCC) criteria and criteria by Heng et al. (J Clin Oncol 2009;27:5794-9), (described here as "VEGF prognostic factors criteria"). The initial post-therapy CT was evaluated by Response Assessment Criteria in Solid Tumors (RECIST), Choi criteria, and Morphology, Attenuation, Size, and Structure (MASS) criteria. Kaplan-Meier estimates of PFS (the reference standard) for each patient group and overall accuracy of each method and combined criteria were calculated. The MSKCC model, VEGF prognostic factors criteria, RECIST, MASS criteria, MSKCC + MASS criteria, and VEGF prognostic factors + MASS criteria each demonstrated significant differences in PFS among patient groups (P therapy clinical risk factors and CT imaging response by MASS criteria more effectively predicted PFS in patients with metastatic RCC on VEGF-targeted therapy than any single method

  5. Response to pediatric physical therapy in infants with positional preference and skull deformation

    NARCIS (Netherlands)

    Wijk, R.M. van; Pelsma, M.; Groothuis-Oudshoorn, C.G.; IJzerman, M.J.; Vlimmeren, L.A. van; Boere-Boonekamp, M.M.

    2014-01-01

    BACKGROUND: Pediatric physical therapy seems to reduce skull deformation in infants with positional preference. However, not all infants show improvement. OBJECTIVE: The study objective was to determine which infant and parent characteristics were related to responses to pediatric physical therapy

  6. Strategies to potentiate immune response after photodynamic therapy (Conference Presentation)

    Science.gov (United States)

    Hamblin, Michael R.

    2017-02-01

    Photodynamic therapy (PDT) has been used as a cancer therapy for forty years but has not yet advanced to a mainstream cancer treatment. Although PDT has been shown to be an efficient photochemical way to destroy local tumors by a combination of non-toxic dyes and harmless visible light, it is its additional effects in mediating the stimulation of the host immune system that gives PDT a great potential to become more widely used. Although the stimulation of tumor-specific cytotoxic T-cells that can destroy distant tumor deposits after PDT has been reported in some animal models, it remains the exception rather than the rule. This realization has prompted several investigators to test various combination approaches that could potentiate the immune recognition of tumor antigens that have been released after PDT. Some of these combination approaches use immunostimulants including various microbial preparations that activate Toll-like receptors and other receptors for pathogen associated molecular patterns. Other approaches use cytokines and growth factors whether directly administered or genetically encoded. A promising approach targets regulatory T-cells. We believe that by understanding the methods employed by tumors to evade immune response and neutralizing them, more precise ways of potentiating PDT-induced immunity can be devised.

  7. Independent evaluation of a clinical prediction rule for spinal manipulative therapy: a randomised controlled trial.

    Science.gov (United States)

    Hancock, Mark J; Maher, Christopher G; Latimer, Jane; Herbert, Robert D; McAuley, James H

    2008-07-01

    A clinical prediction rule to identify patients most likely to respond to spinal manipulation has been published and widely cited but requires further testing for external validity. We performed a pre-planned secondary analysis of a randomised controlled trial investigating the efficacy of spinal manipulative therapy in 239 patients presenting to general practice clinics for acute, non-specific, low back pain. Patients were randomised to receive spinal manipulative therapy or placebo 2 to 3 times per week for up to 4 weeks. All patients received general practitioner care (advice and paracetamol). Outcomes were pain and disability measured at 1, 2, 4 and 12 weeks. Status on the clinical prediction rule was measured at baseline. The clinical prediction rule performed no better than chance in identifying patients with acute, non-specific low back pain most likely to respond to spinal manipulative therapy (pain P = 0.805, disability P = 0.600). At 1-week follow-up, the mean difference in effect of spinal manipulative therapy compared to placebo in patients who were rule positive rather than rule negative was 0.3 points less on a 10-point pain scale (95% CI -0.8 to 1.4). The clinical prediction rule proposed by Childs et al. did not generalise to patients presenting to primary care with acute low back pain who received a course of spinal manipulative therapy.

  8. Fluid responsiveness is predicted by analysis of extra systoles

    DEFF Research Database (Denmark)

    Vistisen, Simon Tilma

    .g. pulse pressure variation). Yet, the idea of a varying preload utilised in dynamic variable monitoring may be useful: The extra systolic post-ectopic beat is associated with increased preload, and I hypothesised that systolic blood pressure (SBP) at the post-ectopic beat could be analysed in relation...... to surrounding sinus beats and that the magnitude of the SBP change (DSBP) could predict fluid responsiveness. OBJECTIVES. To study the hypothesis in post-cardiac surgery patients. METHODS. Patients scheduled for a 500 ml volume expansion were observed. In the time frame, 0-30 min prior to volume expansion, ECG...

  9. Prediction of the thickness of the compensator filter in radiation therapy using computational intelligence

    Energy Technology Data Exchange (ETDEWEB)

    Dehlaghi, Vahab; Taghipour, Mostafa; Haghparast, Abbas [Department of Biomedical Engineering, Kermanshah University of Medical Sciences, Kermanshah (Iran, Islamic Republic of); Roshani, Gholam Hossein [School of Energy, Kermanshah University of Technology, Kermanshah (Iran, Islamic Republic of); Rezaei, Abbas [Department of Electrical Engineering, Kermanshah University of Technology, Kermanshah (Iran, Islamic Republic of); Shayesteh, Sajjad Pashootan [Department of Biomedical Engineering, Kermanshah University of Medical Sciences, Kermanshah (Iran, Islamic Republic of); Adineh-Vand, Ayoub [Department of Computer Engineering, Islamic Azad University, Kermanshah (Iran, Islamic Republic of); Department of Electrical Engineering, Razi University, Kermanshah (Iran, Islamic Republic of); Karimi, Gholam Reza, E-mail: ghkarimi@razi.ac.ir [Department of Electrical Engineering, Razi University, Kermanshah (Iran, Islamic Republic of)

    2015-04-01

    In this study, artificial neural networks (ANNs) and adaptive neuro-fuzzy inference system (ANFIS) are investigated to predict the thickness of the compensator filter in radiation therapy. In the proposed models, the input parameters are field size (S), off-axis distance, and relative dose (D/D{sub 0}), and the output is the thickness of the compensator. The obtained results show that the proposed ANN and ANFIS models are useful, reliable, and cheap tools to predict the thickness of the compensator filter in intensity-modulated radiation therapy.

  10. A biomarker profile for predicting efficacy of cisplatin-vinorelbine therapy in malignant pleural mesothelioma

    DEFF Research Database (Denmark)

    Zimling, Zarah Glad; Sørensen, Jens Benn; Gerds, Thomas Alexander

    2012-01-01

    Malignant pleural mesothelioma (MPM) has a dismal prognosis. Treatment results may be improved by biomarker-directed therapy. We investigated the baseline expression and impact on outcome of predictive biomarkers ERCC1, BRCA1, and class III β-tubulin in a cohort of MPM patients treated with cispl......Malignant pleural mesothelioma (MPM) has a dismal prognosis. Treatment results may be improved by biomarker-directed therapy. We investigated the baseline expression and impact on outcome of predictive biomarkers ERCC1, BRCA1, and class III β-tubulin in a cohort of MPM patients treated...

  11. Dosimetric Inhomogeneity Predicts for Long-Term Breast Pain After Breast-Conserving Therapy

    Energy Technology Data Exchange (ETDEWEB)

    Mak, Kimberley S. [Harvard Radiation Oncology Program, Boston, Massachusetts (United States); Chen, Yu-Hui; Catalano, Paul J. [Department of Biostatistics and Computational Biology, Dana-Farber Cancer Institute, Boston, Massachusetts (United States); Punglia, Rinaa S.; Wong, Julia S.; Truong, Linh [Department of Radiation Oncology, Dana-Farber/Brigham and Women' s Cancer Center, Boston, Massachusetts (United States); Bellon, Jennifer R., E-mail: jbellon@LROC.harvard.edu [Department of Radiation Oncology, Dana-Farber/Brigham and Women' s Cancer Center, Boston, Massachusetts (United States)

    2015-12-01

    Purpose: The objective of this cross-sectional study was to characterize long-term breast pain in patients undergoing breast-conserving surgery and radiation (BCT) and to identify predictors of this pain. Methods and Materials: We identified 355 eligible patients with Tis-T2N0M0 breast cancer who underwent BCT in 2007 to 2011, without recurrent disease. A questionnaire derived from the Late Effects Normal Tissue Task Force (LENT) Subjective, Objective, Management, Analytic (SOMA) scale was mailed with 7 items detailing the severity, frequency, duration, and impact of ipsilateral breast pain over the previous 2 weeks. A logistic regression model identified predictors of long-term breast pain based on questionnaire responses and patient, disease, and treatment characteristics. Results: The questionnaire response rate was 80% (n=285). One hundred thirty-five patients (47%) reported pain in the treated breast, with 19 (14%) having pain constantly or at least daily; 15 (11%) had intense pain. The pain interfered with daily activities in 11 patients (8%). Six patients (4%) took analgesics for breast pain. Fourteen (10%) thought that the pain affected their quality of life. On univariable analysis, volume of breast tissue treated to ≥105% of the prescribed dose (odds ratio [OR] 1.001 per cc, 95% confidence interval [CI] 1.000-1.002; P=.045), volume treated to ≥110% (OR 1.009 per cc, 95% CI 1.002-1.016; P=.012), hormone therapy use (OR 1.95, 95% CI 1.12-3.39; P=.02), and other sites of pain (OR 1.79, 95% CI 1.05-3.07; P=.03) predicted for long-term breast pain. On multivariable analysis, volume ≥110% (OR 1.01 per cc, 95% CI 1.003-1.017; P=.007), shorter time since treatment (OR 0.98 per month, 95% CI 0.96-0.998; P=.03), and hormone therapy (OR 1.84, 95% CI 1.05-3.25; P=.03) were independent predictors of pain. Conclusion: Long-term breast pain was common after BCT. Although nearly half of patients had pain, most considered it tolerable. Dosimetric inhomogeneity

  12. Stimulation of dendritic cells enhances immune response after photodynamic therapy

    Science.gov (United States)

    Mroz, Pawel; Castano, Ana P.; Hamblin, Michael R.

    2009-02-01

    Photodynamic therapy (PDT) involves the administration of photosensitizers followed by illumination of the primary tumor with red light producing reactive oxygen species that cause vascular shutdown and tumor cell necrosis and apoptosis. Anti-tumor immunity is stimulated after PDT due to the acute inflammatory response, priming of the immune system to recognize tumor-associated antigens (TAA). The induction of specific CD8+ Tlymphocyte cells that recognize major histocompatibility complex class I (MHC-I) restricted epitopes of TAAs is a highly desirable goal in cancer therapy. The PDT killed tumor cells may be phagocytosed by dendritic cells (DC) that then migrate to draining lymph nodes and prime naÃve T-cells that recognize TAA epitopes. This process is however, often sub-optimal, in part due to tumor-induced DC dysfunction. Instead of DC that can become mature and activated and have a potent antigen-presenting and immune stimulating phenotype, immature dendritic cells (iDC) are often found in tumors and are part of an immunosuppressive milieu including regulatory T-cells and immunosuppressive cytokines such as TGF-beta and IL10. We here report on the use of a potent DC activating agent, an oligonucleotide (ODN) that contains a non-methylated CpG motif and acts as an agonist of toll like receptor (TLR) 9. TLR activation is a danger signal to notify the immune system of the presence of invading pathogens. CpG-ODN (but not scrambled non-CpG ODN) increased bone-marrow DC activation after exposure to PDT-killed tumor cells, and significantly increased tumor response to PDT and mouse survival after peri-tumoral administration. CpG may be a valuable immunoadjuvant to PDT especially for tumors that produce DC dysfunction.

  13. The utility of fecal calprotectin in predicting the need for escalation of therapy in inflammatory bowel disease.

    Science.gov (United States)

    Kwapisz, Lukasz; Gregor, Jamie; Chande, Nilesh; Yan, Brian; Ponich, Terry; Mosli, Mahmoud

    2017-08-01

    Fecal calprotectin is an important biomarker used in the evaluation of inflammatory bowel disease. It has proven to be an effective tool in initial screening as well monitoring response to therapy. The aim of this study is to examine the utility of fecal calprotectin both as a predictor for the escalation of therapy in established inflammatory bowel disease and as a predictor of de novo diagnosis. Patients with signs and symptoms concerning for inflammatory bowel disease presenting to outpatient clinics were recruited to provide fecal calprotectin stool samples prior to endoscopic evaluation. Patients were followed up for at least one year and monitored clinically for any change in symptomatology, escalation of therapy or development of IBD, confirmed endoscopically. A total of 126 patients, of whom 72 were known to have underlying inflammatory bowel disease, were included in the final analysis. Among the patients with elevated fecal calprotectin levels and known inflammatory bowel disease, 66% (33/50) went on to have escalation of therapy within 12 months compared to 18% (4/22) if the fecal calprotectin levels were in the normal range (p inflammatory bowel disease and a normal endoscopic evaluation, elevated fecal calprotectin resulted in no cases (0/17) of a new diagnosis in the next 12 months. Fecal calprotectin is a useful test for predicting escalation of therapy in established inflammatory bowel disease.

  14. Response to intravenous fentanyl infusion predicts subsequent response to transdermal fentanyl.

    Science.gov (United States)

    Hayashi, Norihito; Kanai, Akifumi; Suzuki, Asaha; Nagahara, Yuki; Okamoto, Hirotsugu

    2016-04-01

    Prediction of the response to transdermal fentanyl (FENtd) before its use for chronic pain is desirable. We tested the hypothesis that the response to intravenous fentanyl infusion (FENiv) can predict the response to FENtd, including the analgesic and adverse effects. The study subjects were 70 consecutive patients with chronic pain. The response to fentanyl at 0.1 mg diluted in 50 ml of physiological saline and infused over 30 min was tested. This was followed by treatment with FENtd (Durotep MT patch 2.1 mg) at a dose of 12.5 µg/h for 2 weeks. Pain intensity before and after FENiv and 2 weeks after FENtd, and the response to treatment, were assessed by the numerical rating scale (NRS), clinical global impression-improvement scale (CGI-I), satisfaction scale (SS), and adverse effects. The NRS score decreased significantly from 7 (4-9) [median (range)] at baseline to 3 (0-8) after FENiv (p 0.04, each). The analgesic and side effects after intravenous fentanyl infusion can be used to predict the response to short-term transdermal treatment with fentanyl.

  15. Alpha-fetoprotein Response Correlates with EASL Response and Survival in Solitary Hepatocellular Carcinoma Treated with Trans-arterial Therapies: A Subgroup Analysis

    Science.gov (United States)

    Memon, Khairuddin; Kulik, Laura; Lewandowski, Robert J; Wang, Edward; Ryu, Robert K; Riaz, Ahsun; Nikolaidis, Paul; Miller, Frank H; Yaghmai, Vahid; Baker, Talia; Abecassis, Michael; Benson, Al B; Mulcahy, Mary F; Omary, Reed A; Salem, Riad

    2012-01-01

    Background and Aims Alpha-fetoprotein (AFP) is a universally recognized tumor marker in hepatocellular carcinoma (HCC). Its utility in assessing response to treatment remains controversial. We sought to study the: a) correlation between AFP response and imaging response, and b) ability of AFP, EASL and WHO response to predict survival outcomes in patients with solitary HCC. Methods 629 HCC patients were treated with transarterial locoregional therapies over an 11-year period. To eliminate confounding factors, we included patients with single tumors, baseline AFP≥200 ng/mL, and no extrahepatic disease; this identified our study cohort of 51 patients. AFP response was defined as >50% decrease from baseline; this was correlated to EASL and WHO response criteria by Kappa agreement, Pearson correlation and receiver operating curves. Survival analyses were performed by Landmark, risk-of-death and Mantel-Byar methodologies. None of the patients received sorafenib. Results Three months post-treatment, AFP and EASL response correlated well (Kappa: 0.83; Pearson: 0.84); the sensitivity, specificity, positive and negative predictive values of AFP in predicting EASL response at 3 months were 96.6%, 85.7%, 92.3% and 93.3% respectively. Correlation with WHO response was low. From the 3-month landmark, WHO, EASL and AFP responders survived longer than nonresponders (P=0.006, 0.0001 and <0.0001 respectively). The risk of death was lower for EASL and AFP responders by both risk-of-death and Mantel-Byar methodologies (P<0.05). Conclusion Response by AFP and EASL are predictors of survival outcome in patients with solitary HCC. AFP correlates with imaging response assessment by EASL guidelines. Achieving AFP response should be one of the therapeutic intents of locoregional therapies. PMID:22245905

  16. Alpha-fetoprotein response correlates with EASL response and survival in solitary hepatocellular carcinoma treated with transarterial therapies: a subgroup analysis.

    Science.gov (United States)

    Memon, Khairuddin; Kulik, Laura; Lewandowski, Robert J; Wang, Edward; Ryu, Robert K; Riaz, Ahsun; Nikolaidis, Paul; Miller, Frank H; Yaghmai, Vahid; Baker, Talia; Abecassis, Michael; Benson, Al B; Mulcahy, Mary F; Omary, Reed A; Salem, Riad

    2012-05-01

    Alpha-fetoprotein (AFP) is a universally recognized tumor marker in hepatocellular carcinoma (HCC). Its utility in assessing response to treatment remains controversial. We sought to study the: (a) correlation between AFP response and imaging response, and (b) ability of AFP, EASL, and WHO response to predict survival outcomes in patients with solitary HCC. Six hundred and twenty-nine HCC patients were treated with transarterial locoregional therapies over an 11-year period. To eliminate confounding factors, we included patients with single tumors, baseline AFP ≥200ng/ml, and no extrahepatic disease; this identified our study cohort of 51 patients. AFP response was defined as>50% decrease from baseline; this was correlated to EASL and WHO response criteria by Kappa agreement, Pearson correlation and receiver operating curves. Survival analyses were performed by Landmark, risk-of-death and Mantel-Byar methodologies. None of the patients received sorafenib. Three months post-treatment, AFP and EASL response correlated well (Kappa: 0.83; Pearson: 0.84); the sensitivity, specificity, positive and negative predictive values of AFP in predicting EASL response at 3 months were 96.6%, 85.7%, 92.3%, and 93.3%, respectively. Correlation with WHO response was low. From the 3-month landmark, WHO, EASL, and AFP responders survived longer than non-responders (p=0.006, 0.0001, and <0.0001, respectively). The risk of death was lower for EASL and AFP responders by both risk-of-death and Mantel-Byar methodologies (p <0.05). Response by AFP and EASL are predictors of survival outcome in patients with solitary HCC. AFP correlates with imaging response assessment by EASL guidelines. Achieving AFP response should be one of the therapeutic intents of locoregional therapies (LRTs). Copyright © 2012 European Association for the Study of the Liver. Published by Elsevier B.V. All rights reserved.

  17. Peripheral endothelial function may predict the effectiveness of beta-blocker therapy in patients with idiopathic dilated cardiomyopathy.

    Science.gov (United States)

    Xie, Xudong; Wu, Bifeng; Chen, Yao; Li, Wenyuan; Hu, Xiaosheng; Chen, Junzhu

    2016-10-15

    Beta-blockers have improved the prognosis of patients with dilated cardiomyopathy as they improve left ventricular (LV) systolic function and structure, which are crucial for myocardial recovery. However, to date, no accurate methods can predict the effectiveness of β-blocker therapy. Our goal was to evaluate whether peripheral endothelial function could be a useful predictor for β-blocker responses and related LV reverse remodeling (LVRR) in patients with idiopathic dilated cardiomyopathy (IDC). Fifty-two IDC patients were recruited and underwent brachial artery flow-mediated dilation (FMD). Beta-blockers were titrated to doses tolerable for each patient. LV function and structure were measured by echocardiography. A positive response to β-blockers was defined as an increase of ≥10% in LV ejection fraction (LVEF). LVRR was defined as an increase of ≥10% in LVEF and a decrease of ≥15% in LV end-systolic volume (LVESV). Baseline FMD was 8.4±3.0% in IDC patients and significantly lower than healthy controls. At three-month follow-up, 54% of patients had a positive β-blocker response and 40% achieved LVRR. Patients with a positive response to β-blockers or with LVRR had significantly higher baseline FMD values than those without. FMD was the most significant predictor of changes in LVEF and LVESV. The sensitivity and specificity of baseline FMD to predict β-blocker responses was 64.3% and 83.3%, respectively, and to predict LVRR was 61.9% and 80.6%, respectively. Beta-blockers themselves did not influence FMD values. FMD could serve as an independent predictor for monitoring β-blocker therapy effectiveness in IDC patients. Copyright © 2016. Published by Elsevier Ireland Ltd.

  18. Auditory brainstem responses to stop consonants predict literacy.

    Science.gov (United States)

    Neef, Nicole E; Schaadt, Gesa; Friederici, Angela D

    2017-03-01

    Precise temporal coding of speech plays a pivotal role in sound processing throughout the central auditory system, which, in turn, influences literacy acquisition. The current study tests whether an electrophysiological measure of this precision predicts literacy skills. Complex auditory brainstem responses were analysed from 62 native German-speaking children aged 11-13years. We employed the cross-phaseogram approach to compute the quality of the electrophysiological stimulus contrast [da] and [ba]. Phase shifts were expected to vary with literacy. Receiver operating curves demonstrated a feasible sensitivity and specificity of the electrophysiological measure. A multiple regression analysis resulted in a significant prediction of literacy by delta cross-phase as well as phonological awareness. A further commonality analysis separated a unique variance that was explained by the physiological measure, from a unique variance that was explained by the behavioral measure, and common effects of both. Despite multicollinearities between literacy, phonological awareness, and subcortical differentiation of stop consonants, a combined assessment of behavior and physiology strongly increases the ability to predict literacy skills. The strong link between the neurophysiological signature of sound encoding and literacy outcome suggests that the delta cross-phase could indicate the risk of dyslexia and thereby complement subjective psychometric measures for early diagnoses. Copyright © 2016 International Federation of Clinical Neurophysiology. Published by Elsevier B.V. All rights reserved.

  19. NEURAL REACTIVITY TO REWARD AS A PREDICTOR OF COGNITIVE BEHAVIORAL THERAPY RESPONSE IN ANXIETY AND DEPRESSION.

    Science.gov (United States)

    Burkhouse, Katie L; Kujawa, Autumn; Kennedy, Amy E; Shankman, Stewart A; Langenecker, Scott A; Phan, K Luan; Klumpp, Heide

    2016-04-01

    Cognitive behavioral therapy (CBT) is a well-established treatment for anxiety and depression; however, response to CBT is heterogeneous across patients and many remain symptomatic after therapy, raising the need to identify prospective predictors for treatment planning. Altered neural processing of reward has been implicated in both depression and anxiety, and improving hedonic capacity is a goal of CBT. However, little is known about how neural response to reward relates to CBT outcomes in depression and anxiety. The current study used the reward positivity (RewP) event-related potential (ERP) component to examine whether neural reactivity to reward would predict CBT response in a sample of patients with anxiety without depression (n = 30) and comorbid anxiety and depression (CAD, n = 22). Participants completed a guessing reward ERP paradigm before completing 12 weeks of standard CBT. The majority of the sample (68%; 35 out of 52 patients) responded to treatment, and those with a reduced RewP at baseline were more likely to respond to treatment. A reduced RewP was also associated with a greater pre-to-post CBT reduction in depressive symptoms among individuals with CAD, but not among individuals with pure anxiety. CBT may be most beneficial in reducing depressive symptoms for individuals who demonstrate decreased reward reactivity prior to treatment. CBT may target reward brain function, leading to greater improvement in symptoms. These effects may be strongest, and therefore most meaningful, for individuals with reward-processing deficits prior to treatment. © 2016 Wiley Periodicals, Inc.

  20. Genetic variability in response to clopidogrel therapy and its clinical implications.

    Science.gov (United States)

    Yukhanyan, Liana; Freynhofer, Matthias K; Siller-Matula, Jolanta; Schrör, Karsten; Huber, Kurt

    2011-05-01

    This article concentrates on individual genetic differences responsible for variations of action of clopidogrel, which have been found to be partially responsible for increased cardiovascular events in patients with coronary artery disease under dual antiplatelet therapy. According to these results, genotyping for the relevant gene polymorphisms, especially for the CYP2C19 loss-of-function alleles, has been discussed to be an effective method of individualising and optimising clopidogrel treatment. However, due to the facts that 1) there are no prospective studies demonstrating a clinical benefit of personalising antiplatelet therapy based on genotyping; 2) CYP2C19 polymorphisms account for only approximately 12% of variability in clopidogrel platelet response; 3) the positive predictive value of CYP2C19 loss-of-function polymorphisms for cardiovascular events in patients with acute coronary syndrome undergoing percutaneous coronary intervention is only approximately 12% - 20%; 4) it is likely that other clinical factors and risk constellations might be of greater clinical importance; and 5) it is unknown whether a specific genetic polymorphism is capable of influencing outcome for the individual patient; genetic profiling cannot be recommended for routine use at present but will remain of considerable scientific interest.

  1. Sustained ERK [corrected] inhibition by EGFR targeting therapies is a predictive factor for synergistic cytotoxicity with PDT as neoadjuvant therapy.

    Science.gov (United States)

    Weyergang, Anette; Selbo, Pål K; Berg, Kristian

    2013-03-01

    Tyrosin kinase inhibitors (TKIs) and monoclonal antibodies aimed to target epidermal growth factor receptor (EGFR) have shown limited effect as monotherapies and drug resistance is a major limitation for therapeutic success. Adjuvant therapies to EGFR targeting therapeutics are therefore of high clinical relevance. Three EGFR targeting drugs, Cetuximab, Erlotinib and Tyrphostin AG1478 were used in combination with photodynamic therapy (PDT) in two EGFR positive cell lines, A-431 epidermoid skin carcinoma and WiDr colorectal adenocarcinoma cells. The amphiphilic meso-tetraphenylporphine with 2 sulphonate groups on adjacent phenyl rings (TPPS(2a)) was utilized as a photosensitizer for PDT. The cytotoxic outcome of the combined treatments was evaluated by cell counting and MTT. Cellular signalling was explored by Western blotting. PDT as neoadjuvant to Tyrphostin in A-431 cells as well as to Tyrphostin or Erlotinib in WiDr cells revealed synergistic cytotoxicity. In contrast, Erlotinib or Cetuximab combined with neoadjuvant PDT induced an antagonistic effect on cell survival of A-431 cells. Neoadjuvant PDT and EGFR targeting therapies induced a synergistic inhibition of ERK as well as synergistic cytotoxicity only when the EGFR targeting monotherapies caused a prolonged ERK inhibition. There were no correlation between EGFR inhibition by the EGFR targeting monotherapies or the combined therapies and the cytotoxic outcome combination-therapies. The results suggest that sustained ERK inhibition by EGFR targeting monotherapies is a predictive factor for synergistic cytotoxicity when combined with neoadjuvant PDT. The present study provides a rationale for selecting anticancer drugs which may benefit from PDT as adjuvant therapy.

  2. Effect of montelukast on excessive airway narrowing response to methacholine in adult asthmatic patients not on controller therapy

    DEFF Research Database (Denmark)

    Ulrik, Charlotte Suppli; Diamant, Zuzana

    2009-01-01

    -response plateau to Mtc in adult asthmatic patients not on controller therapy, and, hence, protects against excessive airway narrowing. Thirty-one asthmatic patients (13 male patients, 18-50 years old; forced expiratory volume in 1 second [FEV(1)], >70% predicted; PD(20), ... of treatment with Mont neither induced a plateau response nor affected maximum FEV(1) response or PD(20). Our findings, therefore, suggest that monotherapy with a LTRA does not protect against excessive airway narrowing in adult asthmatic patients not on inhaled corticosteroids....

  3. Nomogram for predicting symptom severity during radiation therapy for head and neck cancer

    Science.gov (United States)

    Sheu, Tommy; Fuller, Clifton David; Mendoza, Tito R.; Garden, Adam S.; Morrison, William H.; Beadle, Beth, M.; Phan, Jack; Frank, Steven J.; Hanna, Ehab Y.; Lu, Charles; Cleeland, Charles S.; Rosenthal, David I.; Gunn, G. Brandon

    2014-01-01

    Objective Radiation therapy (RT), with or without chemotherapy, can cause significant acute toxicity among patients treated for head & neck cancer (HNC), but predicting, before treatment, who will experience a particular toxicity or symptom is difficult. We created and evaluated two multivariate models and generated a nomogram to predict symptom severity during RT based on a patient-reported outcome (PRO) instrument, the MD Anderson Symptom Inventory–Head&Neck Module (MDASI-HN). Study Design This was a prospective, longitudinal, questionnaire-based study. Setting Tertiary cancer care center. Subjects and Methods Subjects were 264 patients with HNC (mostly oropharyngeal) who had completed the MDASI-HN before and during therapy. Pretreatment variables were correlated with MDASI-HN symptom scores during therapy with multivariate modeling and then correlated with composite MDASI-HN score during week 5 of therapy. Results A multivariate model incorporating pretreatment PROs better predicted MDASI-HN symptom scores during treatment than did a model based on clinical variables and physician-rated patient performance status alone (Aikake information criterion=1442.5 vs. 1459.9). In the most parsimonious model, pretreatment MDASI-HN symptom severity (Ptherapy. Although additional investigation and validation are required, PRO-inclusive prediction tools can be useful for improving symptom interventions and expectations for patients being treated for HNC. PMID:25104816

  4. Value of admission electrocardiogram in predicting outcome of thrombolytic therapy in acute myocardial infarction

    NARCIS (Netherlands)

    F.W.H.M. Bär (Frits); C. de Zwaan (Chris); S.H. Braat (Simon); M.L. Simoons (Maarten); W.T. Hermens (Wim); A. van der Laarse (Arnoud); W.T. Wellens; M. Ramentol; F.W.A. Verheugt (Freek); F. Vermeer (Frank); X.H. Krauss

    1987-01-01

    textabstractTo determine the value of the admission 12-lead electrocardiogram to predict infarct size limitation by thrombolytic therapy, data were analyzed in 488 of 533 patients with acute myocardial infarction (AMI) from a randomized multicenter study. All patients had typical

  5. Interleukin-10 promoter polymorphism predicts initial response of chronic hepatitis B to interferon alfa

    Directory of Open Access Journals (Sweden)

    Ma Weimin

    2011-01-01

    Full Text Available Abstract In order to examine whether variation in interleukin-10 promoter polymorphism would predict the likelihood of sustain response of chronic hepatitis B to treatment with interferon alfa (IFN-α, the inheritance of 3 biallelic polymorphisms in the IL-10 gene promoter in patients with 52 chronic hepatitis B were determined by polymerase chain reaction (PCR-bared techniques, restriction enzyme digestion or direct sequencing. The relationship to the outcome of antiviral therapy for chronic HBV infection was studied in 24 patients who had a virologically sustained response(SR and in 28 non-responder(NR to interferon alfa-2b and several IL-10 variants were more frequent among SR compared with NR. Carriage of the -592A allele, -592A/A genotype and -1082/-1819/-592 ATA haplotype was associated with SR. Our findings indicate that heterogeneity in the promoter region of the IL-10 gene has a role in determining the initial response of chronic hepatitis B to IFN-α therapy.

  6. ETS Gene Fusions as Predictive Biomarkers of Resistance to Radiation Therapy for Prostate Cancer

    Science.gov (United States)

    2016-05-01

    Award  Number:    W81XWH-10-1-0582 TITLE:      ETS Gene Fusions as Predictive Biomarkers of Resistance to Radiation Therapy for Prostate Cancer...5a.  CONTRACT  NUMBER   ETS Gene Fusions as Predictive Biomarkers of Resistance to Radiation Therapy for Prostate Cancer 5b.  GRANT  NUMBER   W81XWH...ramifications,  particularly  in  the  context  of   radiation   therapy ,   which  represents  a  primary  treatment  modality  for  localized  prostate

  7. Music-related reward responses predict episodic memory performance.

    Science.gov (United States)

    Ferreri, Laura; Rodriguez-Fornells, Antoni

    2017-12-01

    Music represents a special type of reward involving the recruitment of the mesolimbic dopaminergic system. According to recent theories on episodic memory formation, as dopamine strengthens the synaptic potentiation produced by learning, stimuli triggering dopamine release could result in long-term memory improvements. Here, we behaviourally test whether music-related reward responses could modulate episodic memory performance. Thirty participants rated (in terms of arousal, familiarity, emotional valence, and reward) and encoded unfamiliar classical music excerpts. Twenty-four hours later, their episodic memory was tested (old/new recognition and remember/know paradigm). Results revealed an influence of music-related reward responses on memory: excerpts rated as more rewarding were significantly better recognized and remembered. Furthermore, inter-individual differences in the ability to experience musical reward, measured through the Barcelona Music Reward Questionnaire, positively predicted memory performance. Taken together, these findings shed new light on the relationship between music, reward and memory, showing for the first time that music-driven reward responses are directly implicated in higher cognitive functions and can account for individual differences in memory performance.

  8. Prediction of higher cost of antiretroviral therapy (ART) according to clinical complexity. A validated clinical index.

    Science.gov (United States)

    Velasco, Cesar; Pérez, Inaki; Podzamczer, Daniel; Llibre, Josep Maria; Domingo, Pere; González-García, Juan; Puig, Inma; Ayala, Pilar; Martín, Mayte; Trilla, Antoni; Lázaro, Pablo; Gatell, Josep Maria

    2016-03-01

    The financing of antiretroviral therapy (ART) is generally determined by the cost incurred in the previous year, the number of patients on treatment, and the evidence-based recommendations, but not the clinical characteristics of the population. To establish a score relating the cost of ART and patient clinical complexity in order to understand the costing differences between hospitals in the region that could be explained by the clinical complexity of their population. Retrospective analysis of patients receiving ART in a tertiary hospital between 2009 and 2011. Factors potentially associated with a higher cost of ART were assessed by bivariate and multivariate analysis. Two predictive models of "high-cost" were developed. The normalized estimated (adjusted for the complexity scores) costs were calculated and compared with the normalized real costs. In the Hospital Index, 631 (16.8%) of the 3758 patients receiving ART were responsible for a "high-cost" subgroup, defined as the highest 25% of spending on ART. Baseline variables that were significant predictors of high cost in the Clinic-B model in the multivariate analysis were: route of transmission of HIV, AIDS criteria, Spanish nationality, year of initiation of ART, CD4+ lymphocyte count nadir, and number of hospital admissions. The Clinic-B score ranged from 0 to 13, and the mean value (5.97) was lower than the overall mean value of the four hospitals (6.16). The clinical complexity of the HIV patient influences the cost of ART. The Clinic-B and Clinic-BF scores predicted patients with high cost of ART and could be used to compare and allocate costs corrected for the patient clinical complexity. Copyright © 2015 Elsevier España, S.L.U. y Sociedad Española de Enfermedades Infecciosas y Microbiología Clínica. All rights reserved.

  9. Anti-tumor immune response after photodynamic therapy

    Science.gov (United States)

    Mroz, Pawel; Castano, Ana P.; Wu, Mei X.; Kung, Andrew L.; Hamblin, Michael R.

    2009-06-01

    Anti-tumor immunity is stimulated after PDT due a number of factors including: the acute inflammatory response caused by PDT, release of antigens from PDT-damaged tumor cells, priming of the adaptive immune system to recognize tumor-associated antigens (TAA), and induction of heat-shock proteins. The induction of specific CD8+ T-lymphocyte cells that recognize major histocompatibility complex class I (MHC-I) restricted epitopes of TAAs is a highly desirable goal in cancer therapy as it would allow the treatment of tumors that may have already metastasized. The PDT killed tumor cells may be phagocytosed by dendritic cells (DC) that then migrate to draining lymph nodes and prime naÃve T-cells that recognize TAA epitopes. We have carried out in vivo PDT with a BPD-mediated vascular regimen using a pair of BALB/c mouse colon carcinomas: CT26 wild type expressing the naturally occurring retroviral antigen gp70 and CT26.CL25 additionally expressing beta-galactosidase (b-gal) as a model tumor rejection antigen. PDT of CT26.CL25 cured 100% of tumors but none of the CT26WT tumors (all recurred). Cured CT26.CL25 mice were resistant to rechallenge. Moreover mice with two bilateral CT26.CL25 tumors that had only one treated with PDT demonstrated spontaneous regression of 70% of untreated contralateral tumors. T-lymphocytes were isolated from lymph nodes of PDT cured mice that recognized a particular peptide specific to b-gal antigen. T-lymphocytes from LN were able to kill CT26.CL25 target cells in vitro but not CT26WT cells as shown by a chromium release assay. CT26.CL25 tumors treated with PDT and removed five days later had higher levels of Th1 cytokines than CT26 WT tumors showing a higher level of immune response. When mice bearing CT26WT tumors were treated with a regimen of low dose cyclophosphamide (CY) 2 days before, PDT led to 100% of cures (versus 0% without CY) and resistance to rechallenge. Low dose CY is thought to deplete regulatory T-cells (Treg, CD4+CD25+foxp

  10. Standard 12-lead electrocardiography measures predictive of increased appropriate therapy in implantable cardioverter defibrillator recipients.

    Science.gov (United States)

    Shi, Bijia; Harding, Scott A; Jimenez, Alejandro; Larsen, Peter D

    2013-06-01

    Identification of patients most likely to benefit from implantable cardioverter defibrillator (ICD) implant remains a complex challenge. This study aimed to investigate the utility of measures derived from standard 10 s 12-lead electrocardiogrphy (ECG) without complex signal processing in predicting appropriate therapy in an ICD population. We examined 108 ICD patients for primary (n = 32) and secondary prevention (n = 76). Baseline clinical data and characteristics of QRS complex, T-wave, and heart rate from standard 12-lead ECG were examined and related to the occurrence of subsequent appropriate therapy. Over a mean follow-up of 29 ± 11 months, 44% of patients received appropriate therapy. Patients with depressed heart rate variability (HRV) (≤6.5%) were 2.68 [95% confidence interval (CI) 1.21-5.90, P = 0.015] times more likely to receive appropriate therapy than patients with HRV >6.5%. In patients with bundle branch block (BBB), large QRS dispersion of >39 ms was associated with 2.88 times risk (95% CI 1.24-6.71, P = 0.014) of experiencing appropriate therapy than those with QRS dispersion 0.4 mV. History of atrial arrhythmia [hazard ratio (HR) = 2.30, 95% CI 1.29-4.12, P = 0.005] and secondary prevention (HR = 2.55, 95% CI 1.14-5.71, P = 0.022) were also predictive of device therapy. Measurements from standard 12-lead ECG were predictive of appropriate therapy in a heterogeneous ICD population. Incorporation of 12-lead ECG parameters such as these into risk stratification models may improve our ability to select patients for ICD implantation.

  11. Is electromyography a predictive test of patient response to biofeedback in the treatment of fecal incontinence?

    Science.gov (United States)

    Lacima, Gloria; Pera, Miguel; González-Argenté, Xavier; Torrents, Abiguei; Valls-Solé, Josep; Espuña-Pons, Montserrat

    2016-03-01

    Biofeedback is effective in more than 70% of patients with fecal incontinence. However, reliable predictors of successful treatment have not been identified. The aim was to identify clinical variables and diagnostic tests, particularly electromyography, that could predict a successful outcome. We included 135 consecutive women with fecal incontinence treated with biofeedback. Clinical evaluation, manometry, ultrasonography, electromyography, and pudendal nerve terminal motor latency were performed before therapy. Treatment outcome was assessed using a symptoms diary, Wexner incontinence score and the patient's subjective perception. According to the symptoms diaries, 106 (78.5%) women had a good clinical result and 29 (21.5%) had a poor result. There were no differences in age, severity and type of fecal incontinence. Maximum resting pressure (39.3 ± 19.1 mmHg vs. 33.7 ± 20.2 mmHg; P = 0.156) and maximum squeeze pressure (91.8 ± 33.2 mmHg vs. 79.8 ± 31.2 mmHg; P = 0.127) were higher in patients having good clinical outcome although the difference was not significant. There were no differences in the presence of sphincter defects or abnormalities in electromyographic recordings. Logistic regression analysis found no independent predictive factor for good clinical outcome. Biofeedback is effective in more than 75% of patients with fecal incontinence. Clinical characteristics of patients and results of baseline tests have no predictive value of response to therapy. Specifically, we found no association between severity of electromyographic deficit and clinical response. © 2015 Wiley Periodicals, Inc.

  12. Predictive Factors for Second-Line Therapy in Metastatic Renal Cell Carcinoma: A Retrospective Analysis

    Directory of Open Access Journals (Sweden)

    Hendrik Eggers

    2017-03-01

    Full Text Available Currently, about 50% of patients with metastatic renal cell carcinoma (mRCC receive a second-line therapy. Therefore, the choice at each subsequent treatment line remains an important issue. In this retrospective study, we sought to identify pretreatment clinical parameters that could predict the likelihood of a patient receiving a second-line therapy. One hundred and sixty-one mRCC patients who received targeted therapy were evaluated. Descriptive statistics, Kaplan–Meier overall survival (OS, Cox regression, and binary logistic regression models were used for data analysis. Second-line therapy was given to 105 patients (65%. Patients with grade 1 tumor received second-line therapy more frequently than those with grade 2/3 tumors (P = 0.03. Only tumor grade was significantly different between patients receiving, or not receiving, second-line treatment. Median OS was significantly superior in patients receiving second-line therapy (32 versus 14 months; P = 0.007; hazard ratio [HR], 1.75; P = 0.008, patients with grade 1 tumors (130 versus 29 months in G2/3 tumors; HR, 3.85; P = 0.009, and in patients without early tumor progression (41 versus 11 months; HR, 5.04; 95% confidence interval [CI], 3.06–8.31; P < 0.001. In binary logistic regression, we identified early progression to be significantly associated with a higher probability of not receiving a second-line therapy (HR, 2.50; 95% CI, 1.01–6.21; P = 0.048. This study hypothesizes that pretreatment grade and early progression are predictive parameters for the selection of patients for second-line therapy.

  13. Block factorization of step response model predictive control problems

    DEFF Research Database (Denmark)

    Kufoalor, D. K.M.; Frison, Gianluca; Imsland, L.

    2017-01-01

    in a traditional manner and use the computationally efficient block factorization facilities in QP solution methods. In order to solve the MPC problem efficiently, both tailored Riccati recursion and condensing algorithms are proposed and embedded into an interior-point method. The proposed algorithms were...... implemented in the HPMPC framework, and the performance is evaluated through simulation studies. The results confirm that a computationally fast controller is achieved, compared to the traditional step response MPC scheme that relies on an explicit prediction formulation. Moreover, the tailored condensing...... algorithm exhibits superior performance and produces solution times comparable to that achieved when using a condensing scheme for an equivalent (but much smaller) state-space model derived from first-principles. Implementation aspects necessary for high performance on embedded platforms are discussed...

  14. Functional response to cholinesterase inhibitor therapy in a naturalistic Alzheimer’s disease cohort

    Directory of Open Access Journals (Sweden)

    Wattmo Carina

    2012-11-01

    Full Text Available Abstract Background Activities of daily living (ADL are an essential part of the diagnostic criteria for Alzheimer’s disease (AD. A decline in ADL affects independent living and has a strong negative impact on caregiver burden. Functional response to cholinesterase inhibitor (ChEI treatment and factors that might influence this response in naturalistic AD patients need investigating. The aim of this study was to identify the socio-demographic and clinical factors that affect the functional response after 6 months of ChEI therapy. Methods This prospective, non-randomised, multicentre study in a routine clinical setting included 784 AD patients treated with donepezil, rivastigmine or galantamine. At baseline and after 6 months of treatment, patients were assessed using several rating scales, including the Instrumental Activities of Daily Living (IADL scale, Physical Self-Maintenance Scale (PSMS and Mini-Mental State Examination (MMSE. Demographic and clinical characteristics were investigated at baseline. The functional response and the relationships of potential predictors were analysed using general linear models. Results After 6 months of ChEI treatment, 49% and 74% of patients showed improvement/no change in IADL and in PSMS score, respectively. The improved/unchanged patients exhibited better cognitive status at baseline; regarding improved/unchanged PSMS, patients were younger and used fewer anti-depressants. A more positive functional response to ChEI was observed in younger individuals or among those having the interaction effect of better preserved cognition and lower ADL ability. Patients with fewer concomitant medications or those using NSAIDs/acetylsalicylic acid showed a better PSMS response. Conclusions Critical characteristics that may influence the functional response to ChEI in AD were identified. Some predictors differed from those previously shown to affect cognitive response, e.g., lower cognitive ability and older age

  15. The evolution of predictive adaptive responses in human life history.

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    Nettle, Daniel; Frankenhuis, Willem E; Rickard, Ian J

    2013-09-07

    Many studies in humans have shown that adverse experience in early life is associated with accelerated reproductive timing, and there is comparative evidence for similar effects in other animals. There are two different classes of adaptive explanation for associations between early-life adversity and accelerated reproduction, both based on the idea of predictive adaptive responses (PARs). According to external PAR hypotheses, early-life adversity provides a 'weather forecast' of the environmental conditions into which the individual will mature, and it is adaptive for the individual to develop an appropriate phenotype for this anticipated environment. In internal PAR hypotheses, early-life adversity has a lasting negative impact on the individual's somatic state, such that her health is likely to fail more rapidly as she gets older, and there is an advantage to adjusting her reproductive schedule accordingly. We use a model of fluctuating environments to derive evolveability conditions for acceleration of reproductive timing in response to early-life adversity in a long-lived organism. For acceleration to evolve via the external PAR process, early-life cues must have a high degree of validity and the level of annual autocorrelation in the individual's environment must be almost perfect. For acceleration to evolve via the internal PAR process requires that early-life experience must determine a significant fraction of the variance in survival prospects in adulthood. The two processes are not mutually exclusive, and mechanisms for calibrating reproductive timing on the basis of early experience could evolve through a combination of the predictive value of early-life adversity for the later environment and its negative impact on somatic state.

  16. Neural responses to exclusion predict susceptibility to social influence.

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    Falk, Emily B; Cascio, Christopher N; O'Donnell, Matthew Brook; Carp, Joshua; Tinney, Francis J; Bingham, C Raymond; Shope, Jean T; Ouimet, Marie Claude; Pradhan, Anuj K; Simons-Morton, Bruce G

    2014-05-01

    Social influence is prominent across the lifespan, but sensitivity to influence is especially high during adolescence and is often associated with increased risk taking. Such risk taking can have dire consequences. For example, in American adolescents, traffic-related crashes are leading causes of nonfatal injury and death. Neural measures may be especially useful in understanding the basic mechanisms of adolescents' vulnerability to peer influence. We examined neural responses to social exclusion as potential predictors of risk taking in the presence of peers in recently licensed adolescent drivers. Risk taking was assessed in a driving simulator session occurring approximately 1 week after the neuroimaging session. Increased activity in neural systems associated with the distress of social exclusion and mentalizing during an exclusion episode predicted increased risk taking in the presence of a peer (controlling for solo risk behavior) during a driving simulator session outside the neuroimaging laboratory 1 week later. These neural measures predicted risky driving behavior above and beyond self-reports of susceptibility to peer pressure and distress during exclusion. These results address the neural bases of social influence and risk taking; contribute to our understanding of social and emotional function in the adolescent brain; and link neural activity in specific, hypothesized, regions to risk-relevant outcomes beyond the neuroimaging laboratory. Results of this investigation are discussed in terms of the mechanisms underlying risk taking in adolescents and the public health implications for adolescent driving. Copyright © 2014 Society for Adolescent Health and Medicine. All rights reserved.

  17. Aggression predicts Cortisol Awakening Response in healthy young adults

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    Patricia Sariñana-González

    2015-10-01

    Full Text Available It seems that aggressive behavior is negatively related to cortisol (C, but this relationship has been established considering the evening C levels. On the other hand, the relationship with the C awakening response (CAR and the influence of gender and menstrual cycle phase are not well understood. This study analyzed this relationship in 83 women (38 in the luteal and 45 in the follicular phase of their menstrual cycle and 20 men. CAR was assessed by measuring salivary free cortisol levels in samples taken immediately following awakening and 30, 45, and 60 minutes later. Additionally, participants completed a self-report of aggression. Men presented lower CAR than women in the luteal phase. Moreover, they also had higher levels of physical aggression than women, independently of their menstrual phase. Regarding the relationships between variables, in men general aggression and verbal aggression predicted the CAR. In women, verbal aggression predicted the CAR during the follicular phase, whereas anger and physical aggression were predictors during the luteal phase. Our data support the view that there is a negative relationship between C and aggressive behavior, even during the morning, this relationship being moderated by gender and menstrual cycle phase in the women. These findings may help improve our understanding of the biological mechanisms involved in violence.

  18. Clinical Examination Does Not Predict Response to Albuterol in Ventilated Infants With Bronchiolitis.

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    Schramm, Craig M; Sala, Kathleen A; Carroll, Christopher L

    2017-01-01

    Bronchiolitis is a common respiratory infection in infants that is sometimes treated with albuterol. Response to albuterol is determined by clinical assessment, but this subjective determination is potentially unreliable. In this study, we compared providers' clinical assessment of response to albuterol with the measurement of response by pulmonary mechanics in intubated, sedated, and ventilated infants. Before and 20 minutes following racemic albuterol therapy, a nurse, respiratory therapist, and physician performed simultaneous examinations and assessed response to albuterol in a population of intubated infants with bronchiolitis. Measurements of ventilator-derived pulmonary mechanics were obtained at these same times. This study was conducted in a PICU of a children's hospital. Seventy-five paired clinical assessments were made in 25 infants who were intubated and mechanically ventilated for severe bronchiolitis. Pulmonary function measurements and clinical assessments before and after administration of albuterol. Response to albuterol was defined using a threshold of improvement in respiratory system resistance from baseline. Nine children (36%) had greater than 20% change and were deemed responders. Providers' discrimination of response was poor. The positive predictive values of nurses, respiratory therapists, and physicians were 38%, 25%, and 25%, respectively, and the negative predictive values were 67%, 54%, and 59%, respectively. Overall accuracy was 44% for nurses, 40% for respiratory therapists, and 48% for physicians. When comparing separate assessments of wheezing, aeration, and expiratory time, there was poor agreement between groups of providers in all variables (κ bronchiolitis. Without assessment of pulmonary mechanics, caution should be used in classifying children with bronchiolitis as responders to albuterol.

  19. Molecular subtypes of metastatic colorectal cancer are associated with patient response to irinotecan-based therapies.

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    Del Rio, M; Mollevi, C; Bibeau, F; Vie, N; Selves, J; Emile, J-F; Roger, P; Gongora, C; Robert, J; Tubiana-Mathieu, N; Ychou, M; Martineau, P

    2017-05-01

    Currently, metastatic colorectal cancer is treated as a homogeneous disease and only RAS mutational status has been approved as a negative predictive factor in patients treated with cetuximab. The aim of this study was to evaluate if recently identified molecular subtypes of colon cancer are associated with response of metastatic patients to first-line therapy. We collected and analysed 143 samples of human colorectal tumours with complete clinical annotations, including the response to treatment. Gene expression profiling was used to classify patients in three to six classes using four different molecular classifications. Correlations between molecular subtypes, response to treatment, progression-free and overall survival were analysed. We first demonstrated that the four previously described molecular classifications of colorectal cancer defined in non-metastatic patients also correctly classify stage IV patients. One of the classifications is strongly associated with response to FOLFIRI (P=0.003), but not to FOLFOX (P=0.911) and FOLFIRI + Bevacizumab (P=0.190). In particular, we identify a molecular subtype representing 28% of the patients that shows an exceptionally high response rate to FOLFIRI (87.5%). These patients have a two-fold longer overall survival (40.1 months) when treated with FOLFIRI, as first-line regimen, instead of FOLFOX (18.6 months). Our results demonstrate the interest of molecular classifications to develop tailored therapies for patients with metastatic colorectal cancer and a strong impact of the first-line regimen on the overall survival of some patients. This however remains to be confirmed in a large prospective clinical trial. Copyright © 2017 Elsevier Ltd. All rights reserved.

  20. Dose- and time-dependence of the host-mediated response to paclitaxel therapy: a mathematical modeling approach.

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    Benguigui, Madeleine; Alishekevitz, Dror; Timaner, Michael; Shechter, Dvir; Raviv, Ziv; Benzekry, Sebastien; Shaked, Yuval

    2018-01-05

    It has recently been suggested that pro-tumorigenic host-mediated processes induced in response to chemotherapy counteract the anti-tumor activity of therapy, and thereby decrease net therapeutic outcome. Here we use experimental data to formulate a mathematical model describing the host response to different doses of paclitaxel (PTX) chemotherapy as well as the duration of the response. Three previously described host-mediated effects are used as readouts for the host response to therapy. These include the levels of circulating endothelial progenitor cells in peripheral blood and the effect of plasma derived from PTX-treated mice on migratory and invasive properties of tumor cells in vitro . A first set of mathematical models, based on basic principles of pharmacokinetics/pharmacodynamics, did not appropriately describe the dose-dependence and duration of the host response regarding the effects on invasion. We therefore provide an alternative mathematical model with a dose-dependent threshold, instead of a concentration-dependent one, that describes better the data. This model is integrated into a global model defining all three host-mediated effects. It not only precisely describes the data, but also correctly predicts host-mediated effects at different doses as well as the duration of the host response. This mathematical model may serve as a tool to predict the host response to chemotherapy in cancer patients, and therefore may be used to design chemotherapy regimens with improved therapeutic outcome by minimizing host mediated effects.

  1. The orthodontist’s civil responsibility post-orthodontic therapy

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    Mayury Kuramae

    2008-01-01

    Full Text Available Objective: The aim of this work was to investigate what the orthodontist’s difficulties are, analyzing whether the adopted procedures are able to satisfy the complaints of individuals, who already concluded orthodontic therapy, according to the determinations of the civil code and the Costumer’s Defense Code, as well as the relationship between patient and professional. Methods: A questionnaire was sent by postal service to all the odonthology specialists inrolled in the CRO/RJ amounting to 990 professionals.Results: The percentual analysis of the analysis showed that 96.9% of them adopt some pattern of kind of contract. The majority (65.8%regards the orthodontist’s Civil Responsibility as a result. In case of reincident postrentation, 87.2% of the professionals inform the individual that it’s possible and also propose them orthodontic re-treatment. Concerning the conduct adopted by the orthodontist towards the individual’s dissatisfaction, 76.5%, anyhow, try to avoid a lawsuit. Conclusion: Some professionals may be subject to future court problems, there was wide divergence between professionals in relation to the time of filing of the orthodontic documentation and there was a relative same opinion of professionals in making an oversight of the patient in the period post-restraint.

  2. Predictive model for the outcome of infliximab therapy in Crohn's disease based on apoptotic pharmacogenetic index and clinical predictors.

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    Hlavaty, Tibor; Ferrante, Marc; Henckaerts, Liesbet; Pierik, Marie; Rutgeerts, Paul; Vermeire, Severine

    2007-04-01

    Infliximab (IFX) is an effective therapy for refractory luminal and fistulizing Crohn's disease (CD). Predictors of response could improve selection of patients with a higher probability of favorable outcomes and could improve the safety profile. We aimed to develop a predictive model for the response to infliximab in CD. Genetic and clinical data collected in a previous pharmacogenetic study of apoptosis genes were analyzed using SAS Enterprise miner modeling software and SPSS 12.0. We proposed a novel apoptotic pharmacogenetic index (API) with a score ranging from 0 (low apoptotic response) to 3 (high apoptotic response) and subsequently developed a decision tree model. Response and remission rates significantly increased with API score (P = 0.005 in the group of patients with luminal CD, P = 0.02 in the group of patients with fistulizing CD). Patients with an API < or = 1 (n = 59) had the lowest response and remission rates in both the luminal CD (50% and 39.5%, respectively) and fistulizing CD (61.9% and 28.6%, respectively) groups, compared to those with an API of 2 (n = 158), whose response and remission rates were 73.8% and 56.1%, respectively, in the luminal CD group and 85.7% and 44.9%, respectively, in the fistulizing CD group; and those with an API of 3 (n = 10), whose response and remission rates were 100% and 85.7%, respectively, in the luminal CD group and 100% and 0% in the fistulizing CD group. Response in patients with an API < or = 1 was significantly influenced by concurrent azathioprine therapy in the luminal CD (21.4% versus 78.9%, P < 0.001) and in the fistulizing CD (46.6% versus 100%, P = 0.04) groups. In patients with an API of 2, we saw an interaction with age older than 40 years and location of disease (response 52.2% versus 83.9%, P = 0.008) in the luminal CD group and with baseline CRP greater than 5 mg/L (73.9% versus 93.9%, P = 0.04) in the fistulizing CD group. From our newly proposed apoptotic pharmacogenetic index and clinical

  3. Personalized medicine in psoriasis: developing a genomic classifier to predict histological response to Alefacept

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    Haider Asifa S

    2010-02-01

    Full Text Available Abstract Background Alefacept treatment is highly effective in a select group patients with moderate-to-severe psoriasis, and is an ideal candidate to develop systems to predict who will respond to therapy. A clinical trial of 22 patients with moderate to severe psoriasis treated with alefacept was conducted in 2002-2003, as a mechanism of action study. Patients were classified as responders or non-responders to alefacept based on histological criteria. Results of the original mechanism of action study have been published. Peripheral blood was collected at the start of this clinical trial, and a prior analysis demonstrated that gene expression in PBMCs differed between responders and non-responders, however, the analysis performed could not be used to predict response. Methods Microarray data from PBMCs of 16 of these patients was analyzed to generate a treatment response classifier. We used a discriminant analysis method that performs sample classification from gene expression data, via "nearest shrunken centroid method". Centroids are the average gene expression for each gene in each class divided by the within-class standard deviation for that gene. Results A disease response classifier using 23 genes was created to accurately predict response to alefacept (12.3% error rate. While the genes in this classifier should be considered as a group, some of the individual genes are of great interest, for example, cAMP response element modulator (CREM, v-MAF avian musculoaponeurotic fibrosarcoma oncogene family (MAFF, chloride intracellular channel protein 1 (CLIC1, also called NCC27, NLR family, pyrin domain-containing 1 (NLRP1, and CCL5 (chemokine, cc motif, ligand 5, also called regulated upon activation, normally T expressed, and presumably secreted/RANTES. Conclusions Although this study is small, and based on analysis of existing microarray data, we demonstrate that a treatment response classifier for alefacept can be created using gene

  4. Influence of the preimplantation QRS axis on responses to cardiac resynchronization therapy.

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    García-Seara, Javier; Martínez-Sande, José L; Cid, Belén; Gude, Francisco; Bastos, María; Domínguez, Miguel; Varela, Alfonso; González-Juanatey, José R

    2008-12-01

    The aim of this study was to determine whether measurement of the QRS axis can help to predict outcome in patients undergoing cardiac resynchronization therapy. The study included 78 patients who had undergone successful cardiac resynchronization device implantation. Patients were classified as having either a normal QRS axis (i.e., between -30 degrees and +120 degrees) or a left QRS axis deviation (i.e., between -30 degrees and -90 degrees). Patients were regarded as responders if they fulfilled all of the following criteria: their functional class improved by at least one grade, their left ventricular ejection fraction increased by at least 5%, they did not need hospitalization for worsening heart failure, and they were still alive at 12-month follow-up. After adjustment for age, preimplantation left ventricular ejection fraction, etiology and mitral regurgitation, a statistically significant interaction was found between the QRS axis and lead location (P=.026). There was a better response with an anterior lead location if the patient had a left QRS axis deviation. A significant interaction was found between the lead location and the preimplantation QRS electrical axis, such that there was a better response to resynchronization therapy when the lead was implanted in the anterior interventricular vein if the patient had a left QRS axis deviation.

  5. Influence of Immune Responses in Gene/Stem Cell Therapies for Muscular Dystrophies

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    Andrea Farini

    2014-01-01

    Full Text Available Muscular dystrophies (MDs are a heterogeneous group of diseases, caused by mutations in different components of sarcolemma, extracellular matrix, or enzymes. Inflammation and innate or adaptive immune response activation are prominent features of MDs. Various therapies under development are directed toward rescuing the dystrophic muscle damage using gene transfer or cell therapy. Here we discussed current knowledge about involvement of immune system responses to experimental therapies in MDs.

  6. Neurocysticercosis as an important differential of paradoxical response during antituberculosis therapy in HIV-negative patient

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    Rivonirina Andry Rakotoarivelo

    2011-12-01

    Full Text Available Neurocysticercosis can simulate a paradoxical response during antituberculosis therapy with neurological ailments. We report the case of a 31 year-old-man, treated for tuberculous meningitis who developed neurological deficit after nine weeks of early antituberculous therapy. The diagnosis of neurocysticercosis was confirmed by CT scan and cerebrospinal fluid analysis. Neurocysticercosis should be sought as an important differential of paradoxical response during antituberculosis therapy.

  7. Complete response to paclitaxel, ifosfamide, and cisplatin therapy in a case of ovarian ependymoma.

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    Hino, Makiko; Kobayashi, Yusuke; Wada, Michiko; Hattori, Yoshihisa; Kurahasi, Takashi; Nakagawa, Hiroyuki

    2016-11-01

    There are many reports on paclitaxel, ifosfamide, and cisplatin (TIP) therapy, following standard bleomycin, etoposide, and cisplatin (BEP) therapy, for salvage treatment of testicular malignant germ cell tumors, but there are no reports on its use for ovarian malignant tumors. We report here that a patient with primary ependymoma of the ovary, who was resistant to BEP therapy, achieved a complete response to a combined therapy, including TIP therapy as the second-line chemotherapy and surgery. This important case, combined with published studies, suggests that TIP therapy is effective for both testicular and ovarian malignant tumors and indicates that TIP therapy can be used as an effective second-line therapy for malignant tumors resistant to BEP therapy. © 2016 Japan Society of Obstetrics and Gynecology.

  8. Diffusion-Weighted Magnetic Resonance Application in Response Prediction before, during, and after Neoadjuvant Radiochemotherapy in Primary Rectal Cancer Carcinoma

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    Daniela Musio

    2013-01-01

    Full Text Available Introduction. Our interest was to monitor treatment response using ADC value to predict response of rectal tumour to preoperative radiochemotherapy. Materials and Methods. Twenty-two patients were treated with long course of radiochemotherapy, followed by surgery. Patients were examined by diffusion-weighted imaging MRI at three-time points (prior, during, and after radiochemotherapy and were classified as responders and nonresponders. Results. A statistical significant correlation was found between preradiochemotherapy ADC values and during treatment ADC values, in responders (F=21.50, P value <0.05. An increase in ADC value during treatment was predictive of at least a partial response. Discussion. Response of tumour to neoadjuvant therapy cannot be easily evaluated, and such capability might be of great importance in clinical practice, because the number of irradiated and operated patients may be superior to the number of who will really benefit from this multimodal treatment. A reliable prediction of the final clinical TN stage would allow radiotherapist to adapt multidisciplinary approach to a less invasive management, sparing surgical procedure in responder patients or even allowing an early surgery in nonresponders, which would significantly reduce radiochemotherapy related toxicity. Conclusion. Early evaluation of response during neoadjuvant radiochemotherapy treatment shows great promise to predict tumour response.

  9. Early trough levels and antibodies to infliximab predict safety and success of reinitiation of infliximab therapy.

    Science.gov (United States)

    Baert, Filip; Drobne, David; Gils, Ann; Vande Casteele, Niels; Hauenstein, Scott; Singh, Sharat; Lockton, Steve; Rutgeerts, Paul; Vermeire, Séverine

    2014-09-01

    Few agents are available for the treatment of inflammatory bowel diseases, and patients frequently become unresponsive to biologics. We investigated the feasibility of reinitiating infliximab therapy for patients who previously received only episodic therapy with, lost response to, or had infusion reactions to infliximab. We also aimed to identify factors associated with the success and safety of restarting infliximab, such as antibodies to infliximab and trough levels of the drug. From the inflammatory bowel disease biobank, we identified 128 consecutive patients (105 patients with Crohn's disease, 23 patients with ulcerative colitis) who restarted infliximab after a median 15-month discontinuation (range, 6-125 mo; 28 patients for loss of response or infusion reactions, 100 patients for remission or pregnancy). We also analyzed serum samples that had been collected during the first period of infliximab therapy (T-1), when therapy was reinitiated (T0), and at later time points (T+1, T+2) for trough levels and antibodies to infliximab. We investigated correlations among response to treatment, infusion reactions, treatment modalities, trough levels, and antibodies to infliximab. Reinitiation of infliximab therapy produced a response in 84.5% of patients at week 14, 70% of patients at 1 year, and in 61% of patients at more than 4 years. Fifteen patients had acute infusion reactions and 10 patients had delayed infusion reactions. The absence of antibodies to infliximab at T+1 (hazard ratio [HR], 0.14; 95% confidence interval [CI], 0.026-0.74; P = .021) and reinitiation with concomitant immunomodulator therapy were associated with short-term responses (HR, 6.0; 95% CI, 1.3-27; P = .019). Pregnancy or remission as reason for discontinuation (HR, 2.70; 95% CI, 1.09-6.67; P = .033) and higher trough levels at T+1 (HR, 2.94; 95% CI, 1.18-7.69; P = .021) were associated with long-term response. Undetectable antibodies to infliximab at T+1 were associated with the safety

  10. Analysis of predictive factors for rapid virologic response in treating patients with chronic hepatitis C

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    ZHANG Dandan

    2014-12-01

    Full Text Available ObjectiveTo analyze the predictive factors for rapid virologic response (RVR in patients with chronic hepatitis C (CHC who received combination therapy with pegylated interferon (PEG-IFN and ribavirin. MethodsA total of 127 CHC patients who were admitted to our department from 2010 to 2012 and received PEG-IFN combined with ribavirin were enrolled in this retrospective cohort study. The patients were divided into RVR group and non-RVR (NRVR group according to their virologic responses after 4 weeks of antiviral therapy. Demographic characteristics and the clinical features prior to treatment were compared between the two groups, and the potential factors that contributed to the acquisition of RVR were analyzed. Comparison of categorical data between groups was made by chi-square test, predictive factors were analyzed by nonparametric test for two independent samples (Mann-Whitney U test, independent predictive factors were tested by univariate and multivariate logistic regression analyses, and the continuous variables of predictive factors were analyzed using receiver operating characteristic curves. ResultsOf the 127 CHC patients, 86 were males and 41 females. There were 11 confirmed cases of liver cirrhosis. There were 100 patients (78.74% who achieved an RVR, and 27 (21.26% with NRVR. Nonparametric analysis showed that eight factors, which were age, time of infection, level of pre-treatment alanine aminotransferase, level of pre-treatment hyaluronic acid, development of hypertension, type of interferon, pathway of infection, and hepatitis C virus (HCV genotype, were significantly different between the RVR and NRVR groups (P<0.05. The logistic regression analysis identified the following factors as independent predictive factors for RVR: non-genotype 1 (OR: 0.203, 95%CI: 0.051-0.802, P<0.05, time of infection (OR: 0.925, 95%CI: 0.868-0.987, P<0.05, and absence of hypertension (OR: 0.129, 95%CI: 0.032-0.521, P<0.05. Conclusion

  11. Factors associated with the clinical response to nonsurgical periodontal therapy in people with type 2 diabetes mellitus.

    Science.gov (United States)

    Michalowicz, Bryan S; Hyman, Leslie; Hou, Wei; Oates, Thomas W; Reddy, Michael; Paquette, David W; Katancik, James A; Engebretson, Steven P

    2014-12-01

    Type 2 diabetes mellitus (T2DM) is a growing health problem worldwide. People with T2DM are at risk of experiencing periodontitis and likely require treatment. Using data from the national multicenter Diabetes and Periodontal Therapy Trial (DPTT), the authors assessed patient-based characteristics associated with the clinical response to nonsurgical therapy. The DPTT investigators randomly assigned adults with T2DM (hemoglobin A1c [HbA1c] ≥ 7 percent and periodontitis to receive immediate or delayed therapy (scaling and root planing, oral hygiene instruction, chlorhexidine rinse). The investigators assessed probing depth (PD), clinical attachment level (CAL), bleeding on probing (BOP), and medical conditions at baseline, three months and six months. Six-month changes in mean PD, CAL and BOP defined the treatment response. Complete data were available for 473 of 514 DPTT participants. The authors used multiple regression models to evaluate participant-level factors associated with the response. More severe baseline PD, CAL and BOP were associated with greater improvements in these same measurements (P 30 kilograms per square meter) experienced greater reductions in PD and BOP than did participants who were not obese (P diabetes duration, and smoking were not associated with change in any outcome (P > .1). In patients with T2DM, baseline disease severity was associated with the clinical response to nonsurgical periodontal therapy. Body mass index and Hispanic ethnicity-but not glycemic control, diabetes duration or smoking-also may be useful in predicting clinical changes in this population.

  12. Insulin-like growth factor 1 receptor and response to anti-IGF1R antibody therapy in osteosarcoma.

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    Yu Cao

    Full Text Available Survival outcomes for patients with osteosarcoma (OS have remained stagnant over the past three decades. Insulin-like growth factor 1 receptor (IGF1R is over-expressed in a number of malignancies, and anti-IGF1R antibodies have and are currently being studied in clinical trials. Understanding the molecular aberrations which result in increased tumor response to anti-IGF1R therapy could allow for the selection of patients most likely to benefit from IGF1R targeted therapy.IGF1R mRNA expression was assessed by RT PCR in OS patient primary tumors, cell lines, and xenograft tumors. IGF1R copy number was assessed by 3 approaches: PCR, FISH, and dot blot analysis. Exons 1-20 of IGF1R were sequenced in xenograft tumors and 87 primary OS tumors, and surface expression of IGF1R was assessed by flow cytometry. Levels of mRNA and protein expression, copy number, and mutation status were compared with tumor response to anti-IGF1R antibody therapy in 4 OS xenograft models.IGF1R mRNA is expressed in OS. Primary patient samples and xenograft samples had higher mRNA expression and copy number compared with corresponding cell lines. IGF1R mRNA expression, cell surface expression, copy number, and mutation status were not associated with tumor responsiveness to anti-IGF1R antibody therapy.IGF1R is expressed in OS, however, no clear molecular markers predict response to IGF1R antibody-mediated therapy. Additional pre-clinical studies assessing potential predictive biomarkers and investigating targetable molecular pathways critical to the proliferation of OS cells are needed.

  13. Incidence, time of occurrence and response to heart failure therapy in patients with anthracycline cardiotoxicity.

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    Khan, Arshad A; Ashraf, Asma; Singh, Rajinder; Rahim, Aadil; Rostom, Walid; Hussain, Mumtaz; Renner, Ian; Collins, Nicholas J

    2017-01-01

    Anthracyclines are commonly used chemotherapeutic medications. In the current analysis, we evaluated all-cause mortality and incidence, timing and response to medical therapy of anthracycline cardiotoxicity. Left ventricular ejection fraction (LVEF) was serially assessed using gated heart pool scan/echocardiography in patients receiving anthracycline-based chemotherapy from January 2009 to December 2014. A total of 1204 patients was administered anthracyclines during the study period. During a median follow up of 32 (interquartile range: 15-58) months, all-cause mortality was 38% (n = 463), with the incidence of cardiotoxicity 10.2% (n = 123). Only 15.4% (n = 19) patients required heart failure hospitalisation, with 48% (n = 59) of patients commenced on beta blockade therapy and/or angiotensin-converting enzyme inhibitors. The majority of patients (73.2%, n = 90) experienced cardiotoxicity within 1 year of anthracycline initiation. The proportion of patients with complete, partial and no LVEF recovery were 16.3% (n = 20), 29.3% (n = 36) and 54.4% (n = 67) respectively. Mortality was higher in the cardiotoxicity group (49% vs 37%, P < 0.01). History of coronary artery disease, leukaemia, idarubicin use and high cumulative anthracycline dose were predictors of cardiotoxicity. Cardiotoxicity after anthracycline use predictably occurs within the first year of therapy and is dose-related, with variable degrees of recovery. While the need for hospitalisation for heart failure was uncommon, medical therapy appears underutilised, suggesting there may be a role for improved surveillance and early initiation of treatment. © 2016 Royal Australasian College of Physicians.

  14. Patient Adherence Predicts Outcome from Cognitive Behavioral Therapy in Obsessive-Compulsive Disorder

    Science.gov (United States)

    Simpson, Helen Blair; Maher, Michael J.; Wang, Yuanjia; Bao, Yuanyuan; Foa, Edna B.; Franklin, Martin

    2011-01-01

    Objective: To examine the effects of patient adherence on outcome from exposure and response prevention (EX/RP) therapy in adults with obsessive-compulsive disorder (OCD). Method: Thirty adults with OCD were randomized to EX/RP (n = 15) or EX/RP augmented by motivational interviewing strategies (n = 15). Both treatments included 3 introductory…

  15. Tumor Response After Stereotactic Body Radiation Therapy to Nonspine Bone Metastases: An Evaluation of Response Criteria

    Energy Technology Data Exchange (ETDEWEB)

    McDonald, Rachel [Department of Radiation Oncology, Sunnybrook Health Sciences Centre, University of Toronto, Toronto, Ontario (Canada); Probyn, Linda [Department of Medical Imaging, Sunnybrook Health Sciences Centre, University of Toronto, Toronto, Ontario (Canada); Poon, Ian; Erler, Darby; Brotherston, Drew; Soliman, Hany; Cheung, Patrick; Chung, Hans; Chu, William; Loblaw, Andrew; Thavarajah, Nemica [Department of Radiation Oncology, Sunnybrook Health Sciences Centre, University of Toronto, Toronto, Ontario (Canada); Lang, Catherine [Department of Medical Imaging, Sunnybrook Health Sciences Centre, University of Toronto, Toronto, Ontario (Canada); Chin, Lee [Department of Physics, Sunnybrook Health Sciences Centre, University of Toronto, Toronto, Ontario (Canada); Chow, Edward, E-mail: Edward.Chow@sunnybrook.ca [Department of Radiation Oncology, Sunnybrook Health Sciences Centre, University of Toronto, Toronto, Ontario (Canada); Sahgal, Arjun [Department of Radiation Oncology, Sunnybrook Health Sciences Centre, University of Toronto, Toronto, Ontario (Canada)

    2015-11-15

    Purpose: To evaluate the applicability of the Response Evaluation Criteria in Solid Tumors (RECIST 1.1) and University of Texas MD Anderson (MDA) Cancer Center criteria in the setting of stereotactic body radiation therapy (SBRT) to nonspine bone metastases. Methods: Patients who were treated with SBRT to nonspine bone metastases were identified by retrospective chart review. An independent musculoskeletal radiologist evaluated response to treatment using computed tomography (CT) scans. Results: Thirty-three patients were treated to 42 nonspine bone metastases. The most common primary cancer cites were renal cell carcinoma (RCC) (33.3%), lung (24.2%), and prostate (18.2%). Bone metastases were either mainly lytic (57.1%), mainly sclerotic (28.6%), or mixed (14.3%). When lytic and sclerotic lesions were evaluated according to RECIST 1.1, local control (LC) was 83%, 85%, 88%, and 80% for those with CT imaging between months 1 to 3, 4 to 6, 7 to 9, and 10 to 12, respectively. When evaluated by the MDA criteria by density, LC within each time period was slightly greater. Overall LC decreased considerably when evaluated by MDA in terms of size. Conclusions: Consensus definitions of response are required as they have implications on clinical trials and disease management. Without consistent response criteria, outcomes from clinical trials cannot be compared and treatment efficacy remains undetermined.

  16. {sup 18}F-Fluorodeoxyglucose Positron Emission Tomography Can Quantify and Predict Esophageal Injury During Radiation Therapy

    Energy Technology Data Exchange (ETDEWEB)

    Niedzielski, Joshua S., E-mail: jsniedzielski@mdanderson.org [Department of Radiation Physics, The University of Texas MD Anderson Cancer Center, Houston, Texas (United States); University of Texas Houston Graduate School of Biomedical Science, Houston, Texas (United States); Yang, Jinzhong [Department of Radiation Physics, The University of Texas MD Anderson Cancer Center, Houston, Texas (United States); University of Texas Houston Graduate School of Biomedical Science, Houston, Texas (United States); Liao, Zhongxing; Gomez, Daniel R. [Department of Radiation Oncology, The University of Texas MD Anderson Cancer Center, Houston, Texas (United States); Stingo, Francesco [Department of Biostatistics, The University of Texas MD Anderson Cancer Center, Houston, Texas (United States); Mohan, Radhe; Martel, Mary K.; Briere, Tina M.; Court, Laurence E. [Department of Radiation Physics, The University of Texas MD Anderson Cancer Center, Houston, Texas (United States); University of Texas Houston Graduate School of Biomedical Science, Houston, Texas (United States)

    2016-11-01

    Purpose: We sought to investigate the ability of mid-treatment {sup 18}F-fluorodeoxyglucose positron emission tomography (PET) studies to objectively and spatially quantify esophageal injury in vivo from radiation therapy for non-small cell lung cancer. Methods and Materials: This retrospective study was approved by the local institutional review board, with written informed consent obtained before enrollment. We normalized {sup 18}F-fluorodeoxyglucose PET uptake to each patient's low-irradiated region (<5 Gy) of the esophagus, as a radiation response measure. Spatially localized metrics of normalized uptake (normalized standard uptake value [nSUV]) were derived for 79 patients undergoing concurrent chemoradiation therapy for non-small cell lung cancer. We used nSUV metrics to classify esophagitis grade at the time of the PET study, as well as maximum severity by treatment completion, according to National Cancer Institute Common Terminology Criteria for Adverse Events, using multivariate least absolute shrinkage and selection operator (LASSO) logistic regression and repeated 3-fold cross validation (training, validation, and test folds). This 3-fold cross-validation LASSO model procedure was used to predict toxicity progression from 43 asymptomatic patients during the PET study. Dose-volume metrics were also tested in both the multivariate classification and the symptom progression prediction analyses. Classification performance was quantified with the area under the curve (AUC) from receiver operating characteristic analysis on the test set from the 3-fold analyses. Results: Statistical analysis showed increasing nSUV is related to esophagitis severity. Axial-averaged maximum nSUV for 1 esophageal slice and esophageal length with at least 40% of axial-averaged nSUV both had AUCs of 0.85 for classifying grade 2 or higher esophagitis at the time of the PET study and AUCs of 0.91 and 0.92, respectively, for maximum grade 2 or higher by treatment completion

  17. Executive Functioning at Baseline Prospectively Predicts Depression Treatment Response.

    Science.gov (United States)

    Dawson, Erica L; Caveney, Angela F; Meyers, Kortni K; Weisenbach, Sara L; Giordani, Bruno; Avery, Erich T; Schallmo, Michael-Paul; Bahadori, Armita; Bieliauskas, Linas A; Mordhorst, Matthew; Marcus, Sheila M; Kerber, Kevin; Zubieta, Jon-Kar; Langenecker, Scott A

    2017-02-09

    Existing cognitive and clinical predictors of treatment response to date are not of sufficient strength to meaningfully impact treatment decision making and are not readily employed in clinical settings. This study investigated whether clinical and cognitive markers used in a tertiary care clinic could predict response to usual treatment over a period of 4 to 6 months in a sample of 75 depressed adults. Patients (N = 384) were sequentially tested in 2 half-day clinics as part of a quality improvement project at an outpatient tertiary care center between August 2003 and September 2007; additional subjects evaluated in the clinic between 2007 and 2009 were also included. Diagnosis was according to DSM-IV-TR criteria and completed by residents and attending faculty. Test scores obtained at intake visits on a computerized neuropsychological screening battery were the Parametric Go/No-Go task and Facial Emotion Perception Task. Treatment outcome was assessed using 9-item Patient Health Questionnaire (PHQ-9) self-ratings at follow-up (n = 75). Usual treatment included psychotropic medication and psychotherapy. Decline in PHQ-9 scores was predicted on the basis of baseline PHQ-9 score and education, with neuropsychological variables entered in the second step. PHQ-9 scores declined by 46% at follow-up (56% responders). Using 2-step multiple regression, baseline PHQ-9 score (P ≤ .05) and education (P ≤ .01) were significant step 1 predictors of percent change in PHQ-9 follow-up scores. In step 2 of the model, faster processing speed with interference resolution (go reaction time) independently explained a significant amount of variance over and above variables in step 1 (12% of variance, P < .01), while other cognitive and affective skills did not. This 2-step model accounted for 28% of the variance in treatment change in PHQ-9 scores. Processing speed with interference resolution also accounted for 12% variance in treatment and follow-up attrition. Use of executive

  18. Effect of cobalt-60 radiation on response to endodontic therapy in monkeys. [Simulation of effects of prior radiotherapy on subsequent dental therapy response

    Energy Technology Data Exchange (ETDEWEB)

    Matson, J.E.; Patterson, S.S.; Kafrawy, A.H.; Hornback, N.B.; Shidnia, H.

    1978-12-01

    Response of teeth that had received therapeutic doses of Cobalt-60 radiation to endodontic therapy were investigated in three monkeys. The results indicated no appreciable effect of the irradiation on the response to root canal treatment aside from reduction in osteoblastic activity.

  19. In vivo imaging using fluorescent antibodies to tumor necrosis factor predicts therapeutic response in Crohn's disease.

    Science.gov (United States)

    Atreya, Raja; Neumann, Helmut; Neufert, Clemens; Waldner, Maximilian J; Billmeier, Ulrike; Zopf, Yurdagül; Willma, Marcus; App, Christine; Münster, Tino; Kessler, Hermann; Maas, Stefanie; Gebhardt, Bernd; Heimke-Brinck, Ralph; Reuter, Eva; Dörje, Frank; Rau, Tilman T; Uter, Wolfgang; Wang, Thomas D; Kiesslich, Ralf; Vieth, Michael; Hannappel, Ewald; Neurath, Markus F

    2014-03-01

    As antibodies to tumor necrosis factor (TNF) suppress immune responses in Crohn's disease by binding to membrane-bound TNF (mTNF), we created a fluorescent antibody for molecular mTNF imaging in this disease. Topical antibody administration in 25 patients with Crohn's disease led to detection of intestinal mTNF(+) immune cells during confocal laser endomicroscopy. Patients with high numbers of mTNF(+) cells showed significantly higher short-term response rates (92%) at week 12 upon subsequent anti-TNF therapy as compared to patients with low amounts of mTNF(+) cells (15%). This clinical response in the former patients was sustained over a follow-up period of 1 year and was associated with mucosal healing observed in follow-up endoscopy. These data indicate that molecular imaging with fluorescent antibodies has the potential to predict therapeutic responses to biological treatment and can be used for personalized medicine in Crohn's disease and autoimmune or inflammatory disorders.

  20. Prediction of Mass Spectral Response Factors from Predicted Chemometric Data for Druglike Molecules

    Science.gov (United States)

    Cramer, Christopher J.; Johnson, Joshua L.; Kamel, Amin M.

    2017-02-01

    A method is developed for the prediction of mass spectral ion counts of drug-like molecules using in silico calculated chemometric data. Various chemometric data, including polar and molecular surface areas, aqueous solvation free energies, and gas-phase and aqueous proton affinities were computed, and a statistically significant relationship between measured mass spectral ion counts and the combination of aqueous proton affinity and total molecular surface area was identified. In particular, through multilinear regression of ion counts on predicted chemometric data, we find that log10(MS ion counts) = -4.824 + c 1•PA + c 2•SA, where PA is the aqueous proton affinity of the molecule computed at the SMD(aq)/M06-L/MIDI!//M06-L/MIDI! level of electronic structure theory, SA is the total surface area of the molecule in its conjugate base form, and c 1 and c 2 have values of -3.912 × 10-2 mol kcal-1 and 3.682 × 10-3 Å-2. On a 66-molecule training set, this regression exhibits a multiple R value of 0.791 with p values for the intercept, c 1, and c 2 of 1.4 × 10-3, 4.3 × 10-10, and 2.5 × 10-6, respectively. Application of this regression to an 11-molecule test set provides a good correlation of prediction with experiment ( R = 0.905) albeit with a systematic underestimation of about 0.2 log units. This method may prove useful for semiquantitative analysis of drug metabolites for which MS response factors or authentic standards are not readily available.

  1. Sialadenitis after radioiodine therapy. Analysis of factors that influence the response to medical treatment.

    Science.gov (United States)

    Geres, Alejandra E; Mereshian, Paula Szafryk; Fernández, Silvia; Rey Caro, Daniel Gonzalo; Castro, Ricardo; Podio, Ricardo; Ojeda, Silvia

    2015-12-01

    To assess the incidence of 131I-induced sialadenitis (SD) in patients with differentiated thyroid cancer (DTC), to analyze clinical and other factors related to metabolic radiotherapy that may predict the lack of response to conventional medical therapy (CMT), and to determine the effectiveness of intraductal steroid instillation in patients failing CMT. Fifty-two patients with DTC, 45 females (86.5%) and 7 males (13.5%) with a mean age of 44.21±13.3 years (r=17-74) who received ablation therapy with 131I after total thyroidectomy. Patients with diseases and/or medication causing xerostomia were excluded. Patients underwent salivary gland scintigraphy with 99Tc (10mCi). Eighteen patients (34.62%) had SD and received antibiotics, antispasmodics, and oral steroids for 15 days. They were divided into two groups: responders to medical therapy (n=12, age 44.3±14.4 years, 2 men [17%], 10 women [83%], cumulative dose 225±167.1 mCi) and non-responders to medical treatment, who underwent steroid instillation into the Stensen's duct (n=6 [33%], 2 men [33%], 4 women [67%], age 50±13.8 years, cumulative dose 138.3±61.7 mCi). Scintigraphy showed damage to the parotid and submaxillary glands. Incidence of 131I-induced sialadenitis was similar to that reported by other authors. Age, mean cumulative dose of 131I, and involvement of parotid and submaxillary glands did not condition response to CMT; however, male sex was a conditioning factor. Symptom persistence for more than 15 days makes instillation into the Stensen's duct advisable. This is an effective and safe method to avoid surgical excision of salivary glands. Copyright © 2015 SEEN. Published by Elsevier España, S.L.U. All rights reserved.

  2. Predicting time to death after withdrawal of life-sustaining therapy.

    Science.gov (United States)

    Munshi, Laveena; Dhanani, Sonny; Shemie, Sam D; Hornby, Laura; Gore, Genevieve; Shahin, Jason

    2015-06-01

    Predicting time to death following the withdrawal of life-sustaining therapy is difficult. Accurate predictions may better prepare families and improve the process of donation after circulatory death. We systematically reviewed any predictive factors for time to death after withdrawal of life support therapy. Fifteen observational studies met our inclusion criteria. The primary outcome was time to death, which was evaluated to be within 60 min in the majority of studies (13/15). Additional time endpoints evaluated included time to death within 30, 120 min, and 10 h, respectively. While most studies evaluated risk factors associated with time to death, a few derived or validated prediction tools. Consistent predictors of time to death that were identified in five or more studies included the following risk factors: controlled ventilation, oxygenation, vasopressor use, Glasgow Coma Scale/Score, and brain stem reflexes. Seven unique prediction tools were derived, validated, or both across some of the studies. These tools, at best, had only moderate sensitivity to predicting the time to death. Simultaneous withdrawal of all support and physician opinion were only evaluated in more recent studies and demonstrated promising predictor capabilities. While the risk factors controlled ventilation, oxygenation, vasopressors, level of consciousness, and brainstem reflexes have been most consistently found to be associated with time to death, the addition of novel predictors, such as physician opinion and simultaneous withdrawal of all support, warrant further investigation. The currently existing prediction tools are not highly sensitive. A more accurate and generalizable tool is needed to inform end-of-life care and enhance the predictions of donation after circulatory death eligibility.

  3. Can Mathematical Models Predict the Outcomes of Prostate Cancer Patients Undergoing Intermittent Androgen Deprivation Therapy?

    Science.gov (United States)

    Everett, R. A.; Packer, A. M.; Kuang, Y.

    Androgen deprivation therapy is a common treatment for advanced or metastatic prostate cancer. Like the normal prostate, most tumors depend on androgens for proliferation and survival but often develop treatment resistance. Hormonal treatment causes many undesirable side effects which significantly decrease the quality of life for patients. Intermittently applying androgen deprivation in cycles reduces the total duration with these negative effects and may reduce selective pressure for resistance. We extend an existing model which used measurements of patient testosterone levels to accurately fit measured serum prostate specific antigen (PSA) levels. We test the model's predictive accuracy, using only a subset of the data to find parameter values. The results are compared with those of an existing piecewise linear model which does not use testosterone as an input. Since actual treatment protocol is to re-apply therapy when PSA levels recover beyond some threshold value, we develop a second method for predicting the PSA levels. Based on a small set of data from seven patients, our results showed that the piecewise linear model produced slightly more accurate results while the two predictive methods are comparable. This suggests that a simpler model may be more beneficial for a predictive use compared to a more biologically insightful model, although further research is needed in this field prior to implementing mathematical models as a predictive method in a clinical setting. Nevertheless, both models are an important step in this direction.

  4. Role of genomic factors beyond thymidylate synthase in the prediction of response to 5-fluorouracil.

    Science.gov (United States)

    Peters, Godefridus J; Smid, K; Meijer, E; van Groeningen, C J; Leon, L G

    2016-12-01

    5-Fluorouracil (5FU) is still a major drug in combinations regimens for the treatment of colorectal cancer (CRC) both in the adjuvant and palliative setting. 5FU or its oral prodrug capecitabine is usually combined with irinotecan/oxaliplatin and the novel agents bevacizumab/cetuximab. Although this improved the outcome, the overall prognosis in patients with metastasized disease is still relatively poor. Although the target for 5FU, thymidylate synthase was shown to have a predictive value, this could only predict response in a subset of patients. Given the heterogeneous and complex nature of CRC, it is likely that other aberrations can affect therapeutic response. As an alternative, we investigated Copy number alterations using oligonucleotide-based high-throughput array-comparative-genomic-hybridization (aCGH) to obtain an unbiased screening of the whole genetic spectrum. Chromosomal aberrations have been identified in 85% of CRC patients and include genomic regions harboring copy number alterations in the DNA. These alterations may change the expression of many genes and might explain the differential response to therapy as shown in recent studies with several 5FU combinations. In order to clarify new predictive parameters for 5FU, we used aCGH in a historical cohort of patients, which received treatment with single agent 5FU, and an unsupervised clustering analysis showed a statistical (p < 0.05) difference between responding and nonresponding patients. We also find that several regions showed differences between responders/non-responders, such as losses in 12p12.3-12q15 and in 18p (where TS is located) in responding patients. Genome-wide analysis may provide an additional tool to discriminate between responders and nonresponders.

  5. Empirically derived personality subtyping for predicting clinical symptoms and treatment response in bulimia nervosa.

    Science.gov (United States)

    Haynos, Ann F; Pearson, Carolyn M; Utzinger, Linsey M; Wonderlich, Stephen A; Crosby, Ross D; Mitchell, James E; Crow, Scott J; Peterson, Carol B

    2017-05-01

    Evidence suggests that eating disorder subtypes reflecting under-controlled, over-controlled, and low psychopathology personality traits constitute reliable phenotypes that differentiate treatment response. This study is the first to use statistical analyses to identify these subtypes within treatment-seeking individuals with bulimia nervosa (BN) and to use these statistically derived clusters to predict clinical outcomes. Using variables from the Dimensional Assessment of Personality Pathology-Basic Questionnaire, K-means cluster analyses identified under-controlled, over-controlled, and low psychopathology subtypes within BN patients (n = 80) enrolled in a treatment trial. Generalized linear models examined the impact of personality subtypes on Eating Disorder Examination global score, binge eating frequency, and purging frequency cross-sectionally at baseline and longitudinally at end of treatment (EOT) and follow-up. In the longitudinal models, secondary analyses were conducted to examine personality subtype as a potential moderator of response to Cognitive Behavioral Therapy-Enhanced (CBT-E) or Integrative Cognitive-Affective Therapy for BN (ICAT-BN). There were no baseline clinical differences between groups. In the longitudinal models, personality subtype predicted binge eating (p = 0.03) and purging (p = 0.01) frequency at EOT and binge eating frequency at follow-up (p = 0.045). The over-controlled group demonstrated the best outcomes on these variables. In secondary analyses, there was a treatment by subtype interaction for purging at follow-up (p = 0.04), which indicated a superiority of CBT-E over ICAT-BN for reducing purging among the over-controlled group. Empirically derived personality subtyping appears to be a valid classification system with potential to guide eating disorder treatment decisions. © 2016 Wiley Periodicals, Inc.(Int J Eat Disord 2017; 50:506-514). © 2016 Wiley Periodicals, Inc.

  6. New genetic biomarkers predicting azathioprine blood concentrations in combination therapy with 5-aminosalicylic acid.

    Science.gov (United States)

    Uchiyama, Kazuhiko; Takagi, Tomohisa; Iwamoto, Yasunori; Kondo, Norihiko; Okayama, Tetsuya; Yoshida, Naohisa; Kamada, Kazuhiro; Katada, Kazuhiro; Handa, Osamu; Ishikawa, Takeshi; Yasuda, Hiroaki; Sakagami, Junichi; Konishi, Hideyuki; Yagi, Nobuaki; Naito, Yuji; Itoh, Yoshito

    2014-01-01

    Azathioprine (AZA) is widely used for the treatment of inflammatory bowel disease (IBD) patients. AZA is catabolized by thiopurine S-methyltransferase (TPMT), which exhibits genetic polymorphisms. It has also been reported that 5-aminosalicylic acid (5-ASA) inhibits TPMT activity, and that increased 6-thioguanine nucleotide (6-TGN, a metabolite of AZA) blood concentrations result in an increased number of ADRs. In this study, single nucleotide polymorphisms (SNPs) related to differential gene expression affecting AZA drug metabolism in combination therapy with 5-ASA were examined. To identify genetic biomarkers for the prediction of 6-TGN blood concentration, ExpressGenotyping analysis was used. ExpressGenotyping analysis is able to detect critical pharmacogenetic SNPs by analyzing drug-induced expression allelic imbalance (EAI) of premature RNA in HapMap lymphocytes. We collected blood samples on 38 patients with inflammatory bowel disease treated with AZA and corroboration of the obtained SNPs was attempted in clinical samples. A large number of SNPs with AZA/5-ASA-induced EAI within the investigated HapMap lymphocytes was identified by ExpressGenotyping analysis. The respective SNPs were analyzed in IBD patients' blood samples. Among these SNPs, several that have not yet been described to be induced by AZA/5-ASA were found. SNPs within SLC38A9 showed a particular correlation with patients' 6-TGN blood concentrations. Based on these results, ExpressGenotyping analysis and genotyping of patients appears to be a useful way to identify inter-individual differences in drug responses and ADRs to AZA/5-ASA. This study provides helpful information on genetic biomarkers for optimized AZA/5-ASA treatment of IBD patients.

  7. Expression of interferon receptor genes (IFNAR1 and IFNAR2 mRNA) in the liver may predict outcome after interferon therapy in patients with chronic genotype 2a or 2b hepatitis C virus infection.

    Science.gov (United States)

    Morita, K; Tanaka, K; Saito, S; Kitamura, T; Kondo, M; Sakaguchi, T; Morimoto, M; Sekihara, H

    1998-03-01

    Hepatitis C virus (HCV) genotype 2a or 2b is associated with a favorable outcome after interferon therapy. However, 19% to 33% of patients do not respond to therapy. We investigated whether interferon receptor gene (IFNAR1 and IFNAR2 mRNA) expression in the liver before interferon therapy predicts long-term response to therapy in patients with genotype 2a or 2b HCV infection. Twenty-seven patients who subsequently received interferon-alpha therapy underwent liver biopsies before interferon therapy. Hepatic IFNAR1 and IFNAR2 mRNA were determined using a reverse transcription-polymerase chain reaction assay. Twenty (74%) patients responded to interferon therapy, while the remaining seven (26%) patients were nonresponders. The expression rates of IFNAR1 and IFNAR2 mRNA in the liver were significantly higher in responders than nonresponders (p IFNAR1 or IFNAR2 mRNA predicted complete response to interferon treatment, with a positive predictive value of 100%. Multiple logistic regression analysis showed that IFNAR1 and/or IFNAR2 mRNA expression was the only significant predictor of the effectiveness of IFN therapy (p = 0.0002). We conclude that expression of interferon receptor genes in the liver is a useful index for predicting the long-term efficacy of interferon therapy in patients with chronic genotype 2a or 2b HCV infection.

  8. Approaches to studying predict academic performance in undergraduate occupational therapy students: a cross-cultural study.

    Science.gov (United States)

    Bonsaksen, Tore; Brown, Ted; Lim, Hua Beng; Fong, Kenneth

    2017-05-02

    Learning outcomes may be a result of several factors including the learning environment, students' predispositions, study efforts, cultural factors and approaches towards studying. This study examined the influence of demographic variables, education-related factors, and approaches to studying on occupational therapy students' Grade Point Average (GPA). Undergraduate occupational therapy students (n = 712) from four countries completed the Approaches and Study Skills Inventory for Students (ASSIST). Demographic background, education-related factors, and ASSIST scores were used in a hierarchical linear regression analysis to predict the students' GPA. Being older, female and more time engaged in self-study activities were associated with higher GPA among the students. In addition, five ASSIST subscales predicted higher GPA: higher scores on 'seeking meaning', 'achieving', and 'lack of purpose', and lower scores on 'time management' and 'fear of failure'. The full model accounted for 9.6% of the variance related to the occupational therapy students' GPA. To improve academic performance among occupational therapy students, it appears important to increase their personal search for meaning and motivation for achievement, and to reduce their fear of failure. The results should be interpreted with caution due to small effect sizes and a modest amount of variance explained by the regression model, and further research on predictors of academic performance is required.

  9. [Identifying predictive factors for therapy nonadherence among hypertensive, older adults from a community in southern Chile].

    Science.gov (United States)

    Mendoza-Parra, Sara; Merino, José Manuel; Barriga, Omar A

    2009-02-01

    To identify the predictive factors associated with therapy nonadherence among hypertensive older adults, based on functional dependency, memory disorders, self-perceived wellbeing, abuse, and depression in an area of southern Chile. A quantitative, exploratory study of a sample of 211 hypertensive, older adults (29.1% of those being treated by the cardiovascular program at the Centro de Salud Familiar San Pedro, in the province of Concepción, del Bío Bío region, Chile). Seven instruments were applied: Pfeiffer's short mental status questionnaire, Yesavage's geriatric depression scale, the elder abuse screening scale, the morale scale of the Philadelphia Geriatric Center, the health behavior scale, the Lawton assessment of instrumental activities of daily living (ADL), and the Katz ADL index. Following an analysis of the important components, latent variables were identified. Two latent variables were identified: social connectedness-measured by the variables depression, abuse, and social satisfaction-and autonomy-measured by the variables mental health and ability to perform basic and instrumental ADLs. These latent variables accounted for 39.7% and 20.7% of nonadherence to therapy, respectively. The latent variables proposed here can be used as predictive factors for therapy nonadherence in elderly adults with arterial hypertension. Causes of nonadherence to therapy cannot be assessed solely at health care centers; but rather, an understanding of the home environment is needed and treatment should be adapted according to the needs that exist there.

  10. Predicting the vibroacoustic response of satellite equipment panels.

    Science.gov (United States)

    Conlon, S C; Hambric, S A

    2003-03-01

    Modern satellites are constructed of large, lightweight equipment panels that are strongly excited by acoustic pressures during launch. During design, performing vibroacoustic analyses to evaluate and ensure the integrity of the complex electronics mounted on the panels is critical. In this study the attached equipment is explicitly addressed and how its properties affect the panel responses is characterized. FEA and BEA methods are used to derive realistic parameters to input to a SEA hybrid model of a panel with multiple attachments. Specifically, conductance/modal density and radiation efficiency for nonhomogeneous panel structures with and without mass loading are computed. The validity of using the spatially averaged conductance of panels with irregular features for deriving the structure modal density is demonstrated. Maidanik's proposed method of modifying the traditional SEA input power is implemented, illustrating the importance of accounting for system internal couplings when calculating the external input power. The predictions using the SEA hybrid model agree with the measured data trends, and are found to be most sensitive to the assumed dynamic mass ratio (attachments/structure) and the attachment internal loss factor. Additional experimental and analytical investigations are recommended to better characterize dynamic masses, modal densities and loss factors.

  11. Investigating the prediction value of multiparametric magnetic resonance imaging at 3 T in response to neoadjuvant chemotherapy in breast cancer

    Energy Technology Data Exchange (ETDEWEB)

    Minarikova, Lenka; Bogner, Wolfgang; Zaric, Olgica; Trattnig, Siegfried; Gruber, Stephan [Medical University of Vienna, High-field MR Centre, Department of Biomedical Imaging and Image-guided Therapy, Vienna (Austria); Christian Doppler Laboratory for Clinical Molecular MR Imaging, Vienna (Austria); Pinker, Katja [Medical University of Vienna, Division of Molecular and Gender Imaging, Department of Biomedical Imaging and Image-guided Therapy, Vienna (Austria); Memorial Sloan-Kettering Cancer Center, Molecular Imaging and Therapy Service, New York, NY (United States); Valkovic, Ladislav [Medical University of Vienna, High-field MR Centre, Department of Biomedical Imaging and Image-guided Therapy, Vienna (Austria); Christian Doppler Laboratory for Clinical Molecular MR Imaging, Vienna (Austria); Slovak Academy of Sciences, Department of Imaging Methods, Institute of Measurement Science, Bratislava (Slovakia); University of Oxford, John Radcliffe Hospital, Oxford Centre for Clinical Magnetic Resonance Research, Oxford (United Kingdom); Bago-Horvath, Zsuzsanna [Medical University of Vienna, Department of Pathology, Comprehensive Cancer Center, Vienna (Austria); Bartsch, Rupert [Medical University of Vienna, Clinical Division of Oncology, Department of Medicine I, Vienna (Austria); Helbich, Thomas H. [Medical University of Vienna, Division of Molecular and Gender Imaging, Department of Biomedical Imaging and Image-guided Therapy, Vienna (Austria)

    2017-05-15

    To explore the predictive value of parameters derived from diffusion-weighted imaging (DWI) and contrast-enhanced (CE)-MRI at different time-points during neoadjuvant chemotherapy (NACT) in breast cancer. Institutional review board approval and written, informed consent from 42 breast cancer patients were obtained. The patients were investigated before and at three different time-points during neoadjuvant chemotherapy (NACT) using tumour diameter and volume from CE-MRI and ADC values obtained from drawn 2D and segmented 3D regions of interest. Prediction of pathologic complete response (pCR) was evaluated using the area under the curve (AUC) of receiver operating characteristic analysis. There was no significant difference between pathologic complete response and non-pCR in baseline size measures (p > 0.39). Diameter change was significantly different in pCR (p < 0.02) before the mid-therapy point. The best predictor was lesion diameter change observed before mid-therapy (AUC = 0.93). Segmented volume was not able to differentiate between pCR and non-pCR at any time-point. The ADC values from 3D-ROI were not significantly different from 2D data (p = 0.06). The best AUC (0.79) for pCR prediction using DWI was median ADC measured before mid-therapy of NACT. The results of this study should be considered in NACT monitoring planning, especially in MRI protocol designing and time point selection. (orig.)

  12. Seasonal Climate Extremes : Mechanism, Predictability and Responses to Global Warming

    Science.gov (United States)

    Shongwe, M. E.

    2010-01-01

    Climate extremes are rarely occurring natural phenomena in the climate system. They often pose one of the greatest environmental threats to human and natural systems. Statistical methods are commonly used to investigate characteristics of climate extremes. The fitted statistical properties are often interpolated or extrapolated to give an indication of the likelihood of a certain event within a given period or interval. Under changing climatic conditions, the statistical properties of climate extremes are also changing. It is an important scientific goal to predict how the properties of extreme events change. To achieve this goal, observational and model studies aimed at revealing important features are a necessary prerequisite. Notable progress has been made in understanding mechanisms that influence climate variability and extremes in many parts of the globe including Europe. However, some of the recently observed unprecedented extremes cannot be fully explained from the already identified forcing factors. A better understanding of why these extreme events occur and their sensitivity to certain reinforcing and/or competing factors is useful. Understanding their basic form as well as their temporal variability is also vital and can contribute to global scientific efforts directed at advancing climate prediction capabilities, particularly making skilful forecasts and realistic projections of extremes. In this thesis temperature and precipitation extremes in Europe and Africa, respectively, are investigated. Emphasis is placed on the mechanisms underlying the occurrence of the extremes, their predictability and their likely response to global warming. The focus is on some selected seasons when extremes typically occur. An atmospheric energy budget analysis for the record-breaking European Autumn 2006 event has been carried out with the goal to identify the sources of energy for the extreme event. Net radiational heating is compared to surface turbulent fluxes of

  13. A Prediction Algorithm for Drug Response in Patients with Mesial Temporal Lobe Epilepsy Based on Clinical and Genetic Information.

    Science.gov (United States)

    Silva-Alves, Mariana S; Secolin, Rodrigo; Carvalho, Benilton S; Yasuda, Clarissa L; Bilevicius, Elizabeth; Alvim, Marina K M; Santos, Renato O; Maurer-Morelli, Claudia V; Cendes, Fernando; Lopes-Cendes, Iscia

    2017-01-01

    Mesial temporal lobe epilepsy is the most common form of adult epilepsy in surgical series. Currently, the only characteristic used to predict poor response to clinical treatment in this syndrome is the presence of hippocampal sclerosis. Single nucleotide polymorphisms (SNPs) located in genes encoding drug transporter and metabolism proteins could influence response to therapy. Therefore, we aimed to evaluate whether combining information from clinical variables as well as SNPs in candidate genes could improve the accuracy of predicting response to drug therapy in patients with mesial temporal lobe epilepsy. For this, we divided 237 patients into two groups: 75 responsive and 162 refractory to antiepileptic drug therapy. We genotyped 119 SNPs in ABCB1, ABCC2, CYP1A1, CYP1A2, CYP1B1, CYP2C9, CYP2C19, CYP2D6, CYP2E1, CYP3A4, and CYP3A5 genes. We used 98 additional SNPs to evaluate population stratification. We assessed a first scenario using only clinical variables and a second one including SNP information. The random forests algorithm combined with leave-one-out cross-validation was used to identify the best predictive model in each scenario and compared their accuracies using the area under the curve statistic. Additionally, we built a variable importance plot to present the set of most relevant predictors on the best model. The selected best model included the presence of hippocampal sclerosis and 56 SNPs. Furthermore, including SNPs in the model improved accuracy from 0.4568 to 0.8177. Our findings suggest that adding genetic information provided by SNPs, located on drug transport and metabolism genes, can improve the accuracy for predicting which patients with mesial temporal lobe epilepsy are likely to be refractory to drug treatment, making it possible to identify patients who may benefit from epilepsy surgery sooner.

  14. Predicting albuminuria response to spironolactone treatment with urinary proteomics in patients with type 2 diabetes and hypertension

    DEFF Research Database (Denmark)

    Lindhardt, Morten; Persson, Frederik; Oxlund, Christina

    2017-01-01

    BACKGROUND: The mineralocorticoid receptor antagonist spironolactone significantly reduces albuminuria in patients with diabetes. Prior studies have shown large between-patient variability in albuminuria treatment response. We previously developed and validated a urinary proteomic classifier...... that predicts onset and progression of chronic kidney disease. Here, we tested whether the proteomic classifier based on 273 urinary peptides (CKD273) predicts albuminuria response to spironolactone treatment. METHODS: We performed a post hoc analysis in a double-blind randomized clinical trial with allocation...... be used to identify individuals with type 2 diabetes who are more likely to show an albuminuria-lowering response to spironolactone treatment. These results suggest that urinary proteomics may be a valuable tool to tailor therapy, but confirmation in a larger clinical trial is required....

  15. Are predictions of cancer response to targeted drugs, based on effects in unrelated tissues, the 'Black Swan' events?

    Science.gov (United States)

    Kurbel, Beatrica; Golem, Ante Zvonimir; Kurbel, Sven

    2015-01-01

    Adverse effects of targeted drugs on normal tissues can predict the cancer response. Rash correlates with efficacy of erlotinib, cetuximab and gefitinib and onset of arterial hypertension with response to bevacizumab, sunitinib, axitinib and sorafenib, possible examples of 'Black Swan' events, unexpected scientific observations, as described by Karl Popper in 1935. The proposition is that our patients have individual intrinsic variants of cell growth control, important for tumor response and adverse effects on tumor-unrelated tissue. This means that the lack of predictive side effects in healthy tissue is linked with poor results of tumor therapy when tumor resistance is caused by mechanisms that protect all cells of that patient from the targeted drug effects.

  16. Effect of montelukast on excessive airway narrowing response to methacholine in adult asthmatic patients not on controller therapy

    DEFF Research Database (Denmark)

    Ulrik, Charlotte Suppli; Diamant, Zuzana

    2009-01-01

    -response plateau to Mtc in adult asthmatic patients not on controller therapy, and, hence, protects against excessive airway narrowing. Thirty-one asthmatic patients (13 male patients, 18-50 years old; forced expiratory volume in 1 second [FEV(1)], >70% predicted; PD(20), ... 2-agonists p.r.n. only with a twice-documented absence of dose-response plateau, participated in a double-blind, parallel study with Mont (10 mg) or placebo once daily for 12 weeks. Mtc dose-response curves (0.03-256 mumol or >40% FEV(1) decline) were repeated every 4 weeks. The primary objective...... of treatment with Mont neither induced a plateau response nor affected maximum FEV(1) response or PD(20). Our findings, therefore, suggest that monotherapy with a LTRA does not protect against excessive airway narrowing in adult asthmatic patients not on inhaled corticosteroids....

  17. Quality of Life in Relation to Pain Response to Radiation Therapy for Painful Bone Metastases

    Energy Technology Data Exchange (ETDEWEB)

    Westhoff, Paulien G., E-mail: p.g.westhoff@umcutrecht.nl [Department of Radiotherapy, University Medical Center Utrecht, Utrecht (Netherlands); Graeff, Alexander de [Department of Medical Oncology, University Medical Center Utrecht, Utrecht (Netherlands); Monninkhof, Evelyn M. [Julius Center for Health Sciences and Primary Care, University Medical Center Utrecht, Utrecht (Netherlands); Pomp, Jacqueline [Department of Radiotherapy, Reinier de Graaf Gasthuis, Delft (Netherlands); Vulpen, Marco van [Department of Radiotherapy, University Medical Center Utrecht, Utrecht (Netherlands); Leer, Jan Willem H. [Department of Radiotherapy, University Medical Center Nijmegen, Nijmegen (Netherlands); Marijnen, Corrie A.M.; Linden, Yvette M. van der [Department of Clinical Oncology, Leiden University Medical Center, Leiden (Netherlands)

    2015-11-01

    Purpose: To study quality of life (QoL) in responders and nonresponders after radiation therapy for painful bone metastases; and to identify factors predictive for a pain response. Patients and Methods: The prospectively collected data of 956 patients with breast, prostate, and lung cancer within the Dutch Bone Metastasis Study were used. These patients, irradiated for painful bone metastases, rated pain, QoL, and overall health at baseline and weekly afterward for 12 weeks. Using generalized estimating equations analysis, the course of QoL was studied, adjusted for primary tumor. To identify predictive variables, proportional hazard analyses were performed, taking into account death as a competing risk, and C-statistics were calculated for discriminative value. Results: In total, 722 patients (76%) responded to radiation therapy. During follow-up, responders had a better QoL in all domains compared with nonresponders. Patients with breast or prostate cancer had a better QoL than patients with lung cancer. In multivariate analysis, baseline predictors for a pain response were breast or prostate cancer as primary tumor, younger age, good performance status, absence of visceral metastases, and using opioids. The discriminative ability of the model was low (C-statistic: 0.56). Conclusions: Responding patients show a better QoL after radiation therapy for painful bone metastases than nonresponders. Our model did not have enough discriminative power to predict which patients are likely to respond to radiation therapy. Therefore, radiation therapy should be offered to all patients with painful bone metastases, aiming to decrease pain and improve QoL.

  18. Unidentified angular recurrent ulceration responsive to antiviral therapy

    Directory of Open Access Journals (Sweden)

    Rahmi Amtha

    2013-03-01

    Full Text Available Background: Recurrent ulcer on angular area is usually called stomatitis angularis. It is caused by many factors such as vertical dimension reduce, vitamin B12, and immune system deficiency, C. albicans and staphylococcus involvement. Clinically is characterized by painful fissure with erythematous base without fever. Purpose: to describe an unidentified angular ulcer proceeded by recurrent ulcers with no response of topical therapy. Case: An 18-years old male came to Oral Medicine clinic in RSCM who complained of angular recurrent ulcers since 3 years ago which developed on skin and bleed easily on mouth opening. Patient had fever before the onset of ulcers. Large, painful, irregular ulcers covered by red crustae on angular area bilaterally. Patient has been treated with various drugs without improvement and lead to mouth opening limitation. Intra oral shows herpetiformtype of ulcer and swollen of gingival. Case management: Provisional diagnosis was established as viral infection thus acyclovir 200 mg five times daily for two weeks and topical anti inflammation gel were administered. Blood test for IgG/IgM of HSV1 and HSV2 were non reactive, however ulceration showed a remarkable improvement. The ulcers healed completely after next 2 weeks with acyclovir. Conclusion: The angular ulceration on above patient failed to fulfill the criteria of stomatitis angularis or herpes labialis lesion. However it showed a good response to antiviral. Therefore, unidentified angular ulceration was appointed, as the lesion might be triggered by other type of human herpes virus or types of virus that response to acyclovir.Latar belakang: ulser rekuren pada sudut mulut biasanya disebut stomatitis angularis. Kelainan ini disebabkan oleh banyak faktor seperti berkurangnya dimensi vertikal, defisiensi vitamin B12 dan sistem kekebalan tubuh, infeksi C. albicans serta staphylococcus. Secara klinis kelainan ini ditandai dengan fisur sakit pada sudut mulut dengan dasar

  19. One-week acid suppression trial in uninvestigated dyspepsia patients with epigastric pain or burning to predict response to 8 weeks' treatment with esomeprazole

    DEFF Research Database (Denmark)

    van Zanten, S V; Flook, N; Talley, N J

    2007-01-01

    BACKGROUND: While empiric acid-suppressive therapy for uninvestigated dyspepsia patients with symptoms of epigastric pain or burning is standard practice, it is unknown whether an early response to therapy predicts outcome. AIM: To evaluate whether a 1-w acid suppression trial is effective for pr...... in patients with symptoms of epigastric pain or burning. Esomeprazole provides greater symptom control than placebo at 4w and 8w....

  20. Factors in Gestational Diabetes Mellitus Predicting the Needs for Insulin Therapy

    Directory of Open Access Journals (Sweden)

    Ya Zhang

    2016-01-01

    Full Text Available Objective. To identify factors predicting the need for insulin therapy in pregnancies complicated by gestational diabetes mellitus (GDM. Methods. A total of 1352 patients with GDM diagnosed by the 75-g/2-h oral glucose tolerance test (OGTT were enrolled in this study. Univariate and multivariate analysis were performed; receiver operating characteristics (ROC were also drawn. Results. There was a significant difference in factors such as maternal age, pregestational BMI, first visit SBP, first visit DBP, FBG of first visit, FBG at time of OGTT, 75-g OGTT glucose value (fasting, after 1 h and 2 h, and serum HbA1c level at diagnosis between patients with insulin therapy and patients with medical nutrition therapy (MNT alone. Multivariate analysis showed that higher FBG at time of OGTT, first 75 g OGTT 2 h plasma glucose, and HbA1c concentration at diagnosis lead to more likely need of insulin therapy. Conclusion. The probability of insulin therapy can be estimated in pregnant women with GDM based on fasting and 2 h glucose values during OGTT and HbA1c value at diagnosis of GDM.

  1. Influence of pacing site characteristics on response to cardiac resynchronization therapy.

    Science.gov (United States)

    Wong, Jorge A; Yee, Raymond; Stirrat, John; Scholl, David; Krahn, Andrew D; Gula, Lorne J; Skanes, Allan C; Leong-Sit, Peter; Klein, George J; McCarty, David; Fine, Nowell; Goela, Aashish; Islam, Ali; Thompson, Terry; Drangova, Maria; White, James A

    2013-07-01

    Transmural scar occupying left ventricular (LV) pacing regions has been associated with reduced response to cardiac resynchronization therapy (CRT). However, spatial influences of lead tip delivery relative to scar at both pacing sites remain poorly explored. This study evaluated scar distribution relative to LV and right ventricular (RV) lead tip placement through coregistration of late gadolinium enhancement MRI and cardiac computed tomographic (CT) findings. Influences on CRT response were assessed by serial echocardiography. Sixty patients receiving CRT underwent preimplant late gadolinium enhancement MRI, postimplant cardiac CT, and serial echocardiography. Blinded segmental evaluations of mechanical delay, percentage scar burden, and lead tip location were performed. Response to CRT was defined as a reduction in LV end-systolic volume ≥15% at 6 months. The mean age and LV ejection fraction were 64±9 years and 25±7%, respectively. Mean scar volume was higher among CRT nonresponders for both the LV (23±23% versus 8±14% [P=0.01]) and RV pacing regions (40±32% versus 24±30% [P=0.04]). Significant pacing region scar was identified in 13% of LV pacing regions and 37% of RV pacing regions. Absence of scar in both regions was associated with an 81% response rate compared with 55%, 25%, and 0%, respectively, when the RV, LV, or both pacing regions contained scar. LV pacing region dyssynchrony was not predictive of response. Myocardial scar occupying the LV pacing region is associated with nonresponse to CRT. Scar occupying the RV pacing region is encountered at higher frequency and seems to provide a more intermediate influence on CRT response.

  2. Magnetic resonance imaging and morphometric histologic analysis of prostate tissue composition in predicting the clinical outcome of terazosin therapy in benign prostatic hyperplasia

    Energy Technology Data Exchange (ETDEWEB)

    Isen, K. [Karaelmas Univ., Zonguldak (Turkey). School of Medicine; Sinik, Z.; Alkibay, T.; Sezer, C.; Soezen, S.; Atilla, S.; Ataoglu, O.; Isik, S.

    2001-02-01

    The purpose of this study was to determine whether magnetic resonance imaging (MRI) or quantitative color-imaged morphometric analysis (MA) of the prostate gland are related to the clinical response to terazosin. Thirty-six male patients with symptomatic benign prostatic hyperplasia (BPH) with a serum prostate-specific antigen level of 4-10 ng/mL underwent MRI with body coil, transrectal prostate unltrasonography and biopsy prior to terazosin therapy. For MRI-determined stromal and non-stromal BPH, the ratio of the signal intensity of the inner gland to the obturator internus muscle was evaluated. Histologic sections were stained with hematoxylin and eosin. The MA of the specimens was performed by Samba 2000. Results of the two techniques were interpreted according to the terazosin therapy results. The mean stromal percentage was 60.5{+-}18.0%. No statistically significant relationship was found between the clinical outcome of terazosin and the MRI findings. The MA results showed a significant relationship between the percentage of stroma and the percent change of the peak urinary flow rate, but not with the percent change of the international prostate symptom score after terazosin therapy (P<0.05). Magnetic resonance imaging alone is not sufficient in predicting the response to terazosin therapy. Morphometric analysis of BPH tissue composition can be used in predicting the clinical outcome of terazosin therapy but it is suitable only in patients for whom prostatic biopsy is necessary in order to rule out prostate cancer. (author)

  3. Perceived therapist genuineness predicts therapeutic alliance in cognitive behavioural therapy for psychosis.

    Science.gov (United States)

    Jung, Esther; Wiesjahn, Martin; Rief, Winfried; Lincoln, Tania M

    2015-03-01

    The quality of therapeutic alliance is a consistent and stable predictor of therapy outcome. Recent studies have shown therapist characteristics to be relevant predictors of the alliance in psychological therapies in general. However, little is known about the specific therapist characteristics that explain differences in therapeutic alliance in cognitive behavioural therapy for psychosis (CBTp). The aim of this study was to identify relevant therapist characteristics that predict early therapeutic alliance in CBTp. Forty-eight patients with a DSM-IV diagnosis of a psychotic disorder participating in a CBTp trial and 11 therapists were included in the analysis. Therapist characteristics as perceived by the patients (empathy, genuineness, positive regard, competence, and convincingness) were assessed at baseline. Alliance was assessed after the fifth therapy session. Data were analyzed using bivariate correlations and multivariate hierarchic regression analysis. All therapist characteristics were positively associated with patient-rated alliance. Patient characteristics were not significantly associated with alliance and did not predict alliance in the multivariate analysis. Regression analysis revealed therapist genuineness and competence to significantly predict higher patient-rated alliance. Our results suggest that perceived therapist genuineness is the most relevant predictor of patient-rated therapeutic alliance in CBTp. Future trials using control samples with other mental disorders could clarify whether this finding is specific to CBTp. Therapist training concepts for increasing beneficial therapist qualities are needed. The patients' perception of the therapist as empathic, genuine, accepting, competent and convincing is associated with therapeutic alliance in CBTp. Perceived therapist genuineness and competence are the most relevant predictors of patient-rated therapeutic alliance. Training and supervision should focus on increasing basic therapist

  4. Predicting Metapopulation Responses To Conservation In Human-Dominated Landscapes

    Directory of Open Access Journals (Sweden)

    Zachary S. Ladin

    2016-10-01

    Full Text Available Loss of habitat to urbanization is a primary cause of population declines as human-dominated landscapes expand at increasing rates. Understanding how the relative effects of different conservation strategies is important to slow population declines for species in urban landscapes. We studied the wood thrush Hylocichla mustelina, a declining forest-breeding Neotropical migratory species, and umbrella species for forest-breeding songbirds, within the urbanized mid-Atlantic United States. We integrated 40 years of demographic data with contemporary metapopulation model simulations of breeding wood thrushes to predict population responses to differing conservation scenarios. We compared four conservation scenarios over a 30-year time period (2014–2044 representing A current observed state (Null, B replacing impervious surface with forest (Reforest, C reducing brown-headed cowbird Molothrus ater parasitism pressure (Cowbird removal, and D simultaneous reforesting and cowbird removal. Compared to the Null scenario, the Reforest scenario increased mean annual population trends by 54 % , the Remove cowbirds scenario increased mean annual population trends by 38 %, and the scenario combining reforestation and cowbird removal increased mean annual population trends by 98 %. Mean annual growth rates (λ per site were greater in the Reforest (λ = 0.94 and Remove cowbirds (λ = 0.92 compared to the Null (λ = 0.88 model scenarios. However, only by combining the positive effects of reforestation and cowbird removal did wood thrush populations stop declining (λ = 1.00. Our results suggest that independently replacing impervious surface with forest habitat around forest patches and removing cowbirds may slow current negative population trends. Furthermore, conservation efforts that combine reforestation and cowbird removal may potentially benefit populations of wood thrushes and other similarly forest-breeding songbird species within urbanized fragmented

  5. Endoscopic and clinical responses to anti-tubercular therapy can differentiate intestinal tuberculosis from Crohn's disease.

    Science.gov (United States)

    Pratap Mouli, V; Munot, K; Ananthakrishnan, A; Kedia, S; Addagalla, S; Garg, S K; Benjamin, J; Singla, V; Dhingra, R; Tiwari, V; Bopanna, S; Hutfless, S; Makharia, G; Ahuja, V

    2017-01-01

    Differentiation between intestinal tuberculosis and Crohn's disease is difficult and may require therapeutic trial with anti-tubercular therapy in tuberculosis-endemic regions. To evaluate the role of therapeutic trial with anti-tubercular therapy in patients with diagnostic confusion between intestinal tuberculosis and Crohn's disease. We performed retrospective-comparative (n = 288: 131 patients who received anti-tubercular therapy before being diagnosed as Crohn's disease and 157 intestinal tuberculosis patients) and prospective-validation study (n = 55 patients with diagnostic confusion of intestinal tuberculosis/Crohn's disease). Outcomes assessed were global symptomatic response and endoscopic mucosal healing. In the derivation cohort, among those eventually diagnosed as Crohn's disease, global symptomatic response with anti-tubercular therapy was seen in 38% at 3 months and in 37% who completed 6 months of anti-tubercular therapy. Ninety-four per cent of intestinal tuberculosis patients showed global symptomatic response by 3 months. Endoscopic mucosal healing was seen in only 5% of patients with Crohn's disease compared with 100% of intestinal tuberculosis patients. In the validation cohort, all the patients with intestinal tuberculosis had symptomatic response and endoscopic mucosal healing after 6 months of anti-tubercular therapy. Among the patients with an eventual diagnosis of Crohn's disease, symptomatic response was seen in 64% at 2 months and in 31% who completed 6 months of anti-tubercular therapy, none had mucosal healing. Disproportionately lower mucosal healing rate despite an overall symptom response with 6 months of anti-tubercular therapy in patients with Crohn's disease suggests a need for repeat colonoscopy for diagnosing Crohn's disease. Patients with intestinal tuberculosis showing significant symptomatic response after 2-3 months of anti-tubercular therapy, suggest that symptom persistence after a therapeutic trial of 3 months of anti

  6. Neural Network Based Response Prediction of rTMS in Major Depressive Disorder Using QEEG Cordance.

    Science.gov (United States)

    Erguzel, Turker Tekin; Ozekes, Serhat; Gultekin, Selahattin; Tarhan, Nevzat; Hizli Sayar, Gokben; Bayram, Ali

    2015-01-01

    The combination of repetitive transcranial magnetic stimulation (rTMS), a non-pharmacological form of therapy for treating major depressive disorder (MDD), and electroencephalogram (EEG) is a valuable tool for investigating the functional connectivity in the brain. This study aims to explore whether pre-treating frontal quantitative EEG (QEEG) cordance is associated with response to rTMS treatment among MDD patients by using an artificial intelligence approach, artificial neural network (ANN). The artificial neural network using pre-treatment cordance of frontal QEEG classification was carried out to identify responder or non-responder to rTMS treatment among 55 MDD subjects. The classification performance was evaluated using k-fold cross-validation. The ANN classification identified responders to rTMS treatment with a sensitivity of 93.33%, and its overall accuracy reached to 89.09%. Area under Receiver Operating Characteristic (ROC) curve (AUC) value for responder detection using 6, 8 and 10 fold cross validation were 0.917, 0.823 and 0.894 respectively. Potential utility of ANN approach method can be used as a clinical tool in administering rTMS therapy to a targeted group of subjects suffering from MDD. This methodology is more potentially useful to the clinician as prediction is possible using EEG data collected before this treatment process is initiated. It is worth using feature selection algorithms to raise the sensitivity and accuracy values.

  7. Dendritic cell vaccination for glioblastoma multiforme: review with focus on predictive factors for treatment response

    Directory of Open Access Journals (Sweden)

    Dejaegher J

    2014-03-01

    Full Text Available Joost Dejaegher,1 Stefaan Van Gool,2 Steven De Vleeschouwer1 1Department of Neurosciences, 2Department of Microbiology and Immunology, KU Leuven, Leuven, Belgium Abstract: Glioblastoma multiforme (GBM is the most common and most aggressive type of primary brain cancer. Since median overall survival with multimodal standard therapy is only 15 months, there is a clear need for additional effective and long-lasting treatments. Dendritic cell (DC vaccination is an experimental immunotherapy being tested in several Phase I and Phase II clinical trials. In these trials, safety and feasibility have been proven, and promising clinical results have been reported. On the other hand, it is becoming clear that not every GBM patient will benefit from this highly personalized treatment. Defining the subgroup of patients likely to respond to DC vaccination will position this option correctly amongst other new GBM treatment modalities, and pave the way to incorporation in standard therapy. This review provides an overview of GBM treatment options and focuses on the currently known prognostic and predictive factors for response to DC vaccination. In this way, it will provide the clinician with the theoretical background to refer patients who might benefit from this treatment. Keywords: immunotherapy, personalized medicine, brain tumor, stratification

  8. Dendritic cell vaccination for glioblastoma multiforme: review with focus on predictive factors for treatment response

    Science.gov (United States)

    Dejaegher, Joost; Van Gool, Stefaan; De Vleeschouwer, Steven

    2014-01-01

    Glioblastoma multiforme (GBM) is the most common and most aggressive type of primary brain cancer. Since median overall survival with multimodal standard therapy is only 15 months, there is a clear need for additional effective and long-lasting treatments. Dendritic cell (DC) vaccination is an experimental immunotherapy being tested in several Phase I and Phase II clinical trials. In these trials, safety and feasibility have been proven, and promising clinical results have been reported. On the other hand, it is becoming clear that not every GBM patient will benefit from this highly personalized treatment. Defining the subgroup of patients likely to respond to DC vaccination will position this option correctly amongst other new GBM treatment modalities, and pave the way to incorporation in standard therapy. This review provides an overview of GBM treatment options and focuses on the currently known prognostic and predictive factors for response to DC vaccination. In this way, it will provide the clinician with the theoretical background to refer patients who might benefit from this treatment. PMID:27471700

  9. Emotional, motivational and interpersonal responsiveness of children with autism in improvisational music therapy

    DEFF Research Database (Denmark)

    Kim, Jinah; Wigram, Tony; Gold, Christian

    2009-01-01

    Through behavioural analysis, this study investigated the social-motivational aspects of musical interaction between the child and the therapist in improvisational music therapy by measuring emotional, motivational and interpersonal responsiveness in children with autism during joint attention ep...... play sessions than music therapy. The results of this exploratory study found significant evidence supporting the value of music therapy in promoting social, emotional and motivational development in children with autism.......Through behavioural analysis, this study investigated the social-motivational aspects of musical interaction between the child and the therapist in improvisational music therapy by measuring emotional, motivational and interpersonal responsiveness in children with autism during joint attention...... episodes. It was a randomized controlled study (n=10) employing a single subject comparison design in two different conditions, improvisational music therapy and toy play sessions and using DVD analysis of sessions.   Improvisational music therapy produced markedly more and longer events of ‘joy...

  10. Scores to predict major bleeding risk during oral anticoagulation therapy: a prospective validation study.

    Science.gov (United States)

    Donzé, Jacques; Rodondi, Nicolas; Waeber, Gérard; Monney, Pierre; Cornuz, Jacques; Aujesky, Drahomir

    2012-11-01

    Clinical scores may help physicians to better assess the individual risk/benefit of oral anticoagulant therapy. We aimed to externally validate and compare the prognostic performance of 7 clinical prediction scores for major bleeding events during oral anticoagulation therapy. We followed 515 adult patients taking oral anticoagulants to measure the first major bleeding event over a 12-month follow-up period. The performance of each score to predict the risk of major bleeding and the physician's subjective assessment of bleeding risk were compared with the C statistic. The cumulative incidence of a first major bleeding event during follow-up was 6.8% (35/515). According to the 7 scoring systems, the proportions of major bleeding ranged from 3.0% to 5.7% for low-risk, 6.7% to 9.9% for intermediate-risk, and 7.4% to 15.4% for high-risk patients. The overall predictive accuracy of the scores was poor, with the C statistic ranging from 0.54 to 0.61 and not significantly different from each other (P=.84). Only the Anticoagulation and Risk Factors in Atrial Fibrillation score performed slightly better than would be expected by chance (C statistic, 0.61; 95% confidence interval, 0.52-0.70). The performance of the scores was not statistically better than physicians' subjective risk assessments (C statistic, 0.55; P=.94). The performance of 7 clinical scoring systems in predicting major bleeding events in patients receiving oral anticoagulation therapy was poor and not better than physicians' subjective assessments. Copyright © 2012 Elsevier Inc. All rights reserved.

  11. The combined use of disease activity and infliximab serum trough concentrations for early prediction of (non-)response to infliximab in rheumatoid arthritis

    Science.gov (United States)

    van den Bemt, Bart J F; den Broeder, Alfons A; Wolbink, Gert-Jan; van den Maas, Aatke; Hekster, Yechiel A; van Riel, Piet L C M; Benraad, H Bart; van den Hoogen, Frank H J

    2013-01-01

    Aim Early prediction of (non-)response to infliximab therapy can improve therapeutic benefit by avoiding unnecessary periods of high disease activity during ineffective therapy. This prospective cohort study therefore aimed to study the predictive value of (1) disease activity alone and (2) infliximab serum trough concentrations in addition to disease activity 6 weeks after start of treatment for achieving low disease activity after 6 months. Methods Disease activity and infliximab serum trough concentrations were assessed in all rheumatoid arthritis (RA) patients at 2, 6 and 26 weeks after initiation of infliximab therapy. Receiver operating characteristic (ROC) curves and Youden indices were used to calculate specificity for prediction of good response after 6 months while aiming for maximum sensitivity. Results Fifty-seven consecutive RA patients starting with infliximab therapy were included. After 6 months, 15 (26%, 95 % CI 15, 38%) patients reached good European League against Rheumatism (EULAR) response. A disease activity score Infliximab serum trough concentrations (>2.5 mg l−1) as predictor complimentary to disease activity (infliximab serum trough concentrations could be a fair predictor to identify early (after 6 weeks) patients who have insufficient response after 6 months of therapy. PMID:23601129

  12. Cell adhesion molecules and hyaluronic acid as markers of inflammation, fibrosis and response to antiviral therapy in chronic hepatitis C patients

    Directory of Open Access Journals (Sweden)

    Esther Granot

    2001-01-01

    Full Text Available Objective: Cell adhesion molecules (intracellular adhesion molecule-1 (ICAM-1, vascular cell adhesion molecule-1 (VCAM-1 and hyaluronic acid, markers of inflammation and fibrosis were monitored in hepatitis C patients to determine whether changes in plasma levels, during antiviral treatment, can predict long-term response to therapy.

  13. Predicted Rates of Secondary Malignancies From Proton Versus Photon Radiation Therapy for Stage I Seminoma

    Energy Technology Data Exchange (ETDEWEB)

    Simone, Charles B., E-mail: csimone@alumni.upenn.edu [Department of Radiation Oncology, Hospital of University of Pennsylvania, Philadelphia, Pennsylvania (United States); Radiation Oncology Branch, National Cancer Institute, National Institutes of Health, Bethesda, Maryland (United States); Kramer, Kevin [Henry M. Jackson Foundation for the Advancement of Military Medicine, Rockville, Maryland (United States); O' Meara, William P. [Division of Radiation Oncology, National Naval Medical Center, Bethesda, Maryland (United States); Bekelman, Justin E. [Department of Radiation Oncology, Hospital of University of Pennsylvania, Philadelphia, Pennsylvania (United States); Belard, Arnaud [Henry M. Jackson Foundation for the Advancement of Military Medicine, Rockville, Maryland (United States); McDonough, James [Department of Radiation Oncology, Hospital of University of Pennsylvania, Philadelphia, Pennsylvania (United States); O' Connell, John [Radiation Oncology Service, Walter Reed Army Medical Center, Washington, DC (United States)

    2012-01-01

    Purpose: Photon radiotherapy has been the standard adjuvant treatment for stage I seminoma. Single-dose carboplatin therapy and observation have emerged as alternative options due to concerns for acute toxicities and secondary malignancies from radiation. In this institutional review board-approved study, we compared photon and proton radiotherapy for stage I seminoma and the predicted rates of excess secondary malignancies for both treatment modalities. Methods and Material: Computed tomography images from 10 consecutive patients with stage I seminoma were used to quantify dosimetric differences between photon and proton therapies. Structures reported to be at increased risk for secondary malignancies and in-field critical structures were contoured. Reported models of organ-specific radiation-induced cancer incidence rates based on organ equivalent dose were used to determine the excess absolute risk of secondary malignancies. Calculated values were compared with tumor registry reports of excess secondary malignancies among testicular cancer survivors. Results: Photon and proton plans provided comparable target volume coverage. Proton plans delivered significantly lower mean doses to all examined normal tissues, except for the kidneys. The greatest absolute reduction in mean dose was observed for the stomach (119 cGy for proton plans vs. 768 cGy for photon plans; p < 0.0001). Significantly more excess secondary cancers per 10,000 patients/year were predicted for photon radiation than for proton radiation to the stomach (4.11; 95% confidence interval [CI], 3.22-5.01), large bowel (0.81; 95% CI, 0.39-1.01), and bladder (0.03; 95% CI, 0.01-0.58), while no difference was demonstrated for radiation to the pancreas (0.02; 95% CI, -0.01-0.06). Conclusions: For patients with stage I seminoma, proton radiation therapy reduced the predicted secondary cancer risk compared with photon therapy. We predict a reduction of one additional secondary cancer for every 50 patients

  14. The neurophysiological response to manual therapy and its analgesic implications: A narrative review

    OpenAIRE

    Andrew D. Vigotsky; Bruhns, Ryan P.

    2015-01-01

    Manual therapy has long been a component of physical rehabilitation programs, especially to treat those in pain. The mechanisms of manual therapy, however, are not fully understood, and it has been suggested that its pain modulatory effects are of neurophysiological origin, and may be mediated by the descending modulatory circuit. Therefore, the purpose of this review is to examine the neurophysiological response of different types of manual therapy, in order to better understand the neurophy...

  15. Caregiver Report of Child Symptoms Predicts Attrition in Abuse-Specific Cognitive Behavioral Therapies.

    Science.gov (United States)

    Tebbett, Alison A; Brown, Elissa J; Chaplin, William F

    2017-01-01

    A common critique of empirically supported treatments for abuse-related psychopathology is attrition during critical phases of therapy (i.e., exposure). The goal of this study was to examine whether child and caregiver symptoms were predictive of attrition among families in abuse-specific cognitive-behavioral therapies (CBTs). Children ( N = 104) and their caregivers completed baseline assessments of internalizing symptoms, externalizing problems, and post-traumatic stress disorder (PTSD) and were enrolled in abuse-specific CBTs. Logistic regressions were conducted with baseline symptoms as predictor variables and treatment status (attrition vs. completion) as the criterion variable. Caregiver report of child internalizing symptoms showed the predicted quadratic relation to attrition. Caregiver report of child externalizing symptoms at moderate and high (vs. low) levels was associated with attrition. Child self-report and caregiver self-report of symptoms were not associated with the dyad's attrition. These results underscore the importance of attending to caregivers' initial perceptions of children's symptoms in abuse-specific therapy.

  16. The Use of Factorial Forecasting to Predict Public Response

    Science.gov (United States)

    Weiss, David J.

    2012-01-01

    Policies that call for members of the public to change their behavior fail if people don't change; predictions of whether the requisite changes will take place are needed prior to implementation. I propose to solve the prediction problem with Factorial Forecasting, a version of functional measurement methodology that employs group designs. Aspects…

  17. Chemotherapy of colorectal liver metastases induces a rapid rise in intermediate blood monocytes which predicts treatment response

    Science.gov (United States)

    Schauer, Dominic; Starlinger, Patrick; Alidzanovic, Lejla; Zajc, Philipp; Maier, Thomas; Feldman, Alexandra; Padickakudy, Robin; Buchberger, Elisabeth; Elleder, Vanessa; Spittler, Andreas; Stift, Judith; Pop, Lorand; Gruenberger, Birgit; Gruenberger, Thomas; Brostjan, Christine

    2016-01-01

    ABSTRACT We have previously reported that intermediate monocytes (CD14++/CD16+) were increased in colorectal cancer (CRC) patients, while the subset of pro-angiogenic TIE2-expressing monocytes (TEMs) was not significantly elevated. This study was designed to evaluate changes in frequency and function of intermediate monocytes and TEMs during chemotherapy and anti-angiogenic cancer treatment and their relation to treatment response. Monocyte populations were determined by flow cytometry in 60 metastasized CRC (mCRC) patients who received neoadjuvant chemotherapy with or without bevacizumab. Blood samples were taken before treatment, after two therapy cycles, at the end of neoadjuvant therapy and immediately before surgical resection of liver metastases. Neoadjuvant treatment resulted in a significant increase in circulating intermediate monocytes which was most pronounced after two cycles and positively predicted tumor response (AUC = 0.875, p = 0.005). With a cut-off value set to 1% intermediate monocytes of leukocytes, this parameter showed a predictive sensitivity and specificity of 75% and 88%. Anti-angiogenic therapy with bevacizumab had no impact on monocyte populations including TEMs. In 15 patients and six healthy controls, the gene expression profile and the migratory behavior of monocyte subsets was evaluated. The profile of intermediate monocytes suggested functions in antigen presentation, inflammatory cytokine production, chemotaxis and was remarkably stable during chemotherapy. Intermediate monocytes showed a preferential migratory response to tumor-derived signals in vitro and correlated with the level of CD14+/CD16+ monocytic infiltrates in the resected tumor tissue. In conclusion, the rapid rise of intermediate monocytes during chemotherapy may offer a simple marker for response prediction and a timely change in regimen. PMID:27471631

  18. PREDICTS: Projecting Responses of Ecological Diversity in Changing Terrestrial Systems

    Directory of Open Access Journals (Sweden)

    Georgina Mace

    2012-12-01

    Full Text Available The PREDICTS project (www.predicts.org.uk is a three-year NERC-funded project to model and predict at a global scale how local terrestrial diversity responds to human pressures such as land use, land cover, pollution, invasive species and infrastructure. PREDICTS is a collaboration between Imperial College London, the UNEP World Conservation Monitoring Centre, Microsoft Research Cambridge, UCL and the University of Sussex. In order to meet its aims, the project relies on extensive data describing the diversity and composition of biological communities at a local scale. Such data are collected on a vast scale through the committed efforts of field ecologists. If you have appropriate data that you would be willing to share with us, please get in touch (enquiries@predicts.org.uk. All contributions will be acknowledged appropriately and all data contributors will be included as co-authors on an open-access paper describing the database.

  19. Stochastic Predictions of Cell Kill During Stereotactic Ablative Radiation Therapy: Do Hypoxia and Reoxygenation Really Matter?

    Energy Technology Data Exchange (ETDEWEB)

    Harriss-Phillips, Wendy M., E-mail: wharrphil@gmail.com [Department of Medical Physics, Royal Adelaide Hospital, Adelaide, South Australia (Australia); School of Chemistry and Physics, University of Adelaide, Adelaide, South Australia (Australia); Bezak, Eva [School of Chemistry and Physics, University of Adelaide, Adelaide, South Australia (Australia); International Centre for Allied Health Evidence, University of South Australia, Adelaide, South Australia (Australia); Sansom Institute for Health Research, University of South Australia, Adelaide, South Australia (Australia); Potter, Andrew [Department of Radiation Oncology, Royal Adelaide Hospital, Adelaide, South Australia (Australia); Adelaide Radiotherapy Centre, Genesis CancerCare, Adelaide, South Australia (Australia)

    2016-07-15

    Purpose: To simulate stereotactic ablative radiation therapy on hypoxic and well-oxygenated in silico tumors, incorporating probabilistic parameter distributions and linear-quadratic versus linear-quadratic-cubic methodology and the evaluation of optimal fractionation schemes using biological effective dose (BED{sub α/β=10} {sub or} {sub 3}) comparisons. Methods and Materials: A temporal tumor growth and radiation therapy algorithm simulated high-dose external beam radiation therapy using stochastic methods. Realistic biological proliferative cellular hierarchy and pO{sub 2} histograms were incorporated into the 10{sup 8}-cell tumor model, with randomized radiation therapy applied during continual cell proliferation and volume-based gradual tumor reoxygenation. Dose fractions ranged from 6-35 Gy, with predictive outcomes presented in terms of the total doses (converted to BED) required to eliminate all cells that could potentially regenerate the tumor. Results: Well-oxygenated tumor control BED{sub 10} outcomes were not significantly different for high-dose versus conventional radiation therapy (BED{sub 10}: 79-84 Gy; Equivalent Dose in 2 Gy fractions with α/β of 10: 66-70 Gy); however, total treatment times decreased from 7 down to 1-3 weeks. For hypoxic tumors, an additional 28 Gy (51 Gy BED{sub 10}) was required, with BED{sub 10} increasing with dose per fraction due to wasted dose in the final fraction. Fractions of 9 Gy compromised well for total treatment time and BED, with BED{sub 10}:BED{sub 3} of 84:176 Gy for oxic and 132:278 Gy for non-reoxygenating hypoxic tumors. Initial doses of 12 Gy followed by 6 Gy further increased the therapeutic ratio. When delivering ≥9 Gy per fraction, applying reoxygenation and/or linear-quadratic-cubic cell survival both affected tumor control doses by a significant 1-2 fractions. Conclusions: The complex temporal dynamics of tumor oxygenation combined with probabilistic cell kinetics in the modeling of

  20. Personality and Differential Treatment Response in Major Depression: A Randomized Controlled Trial Comparing Cognitive-Behavioural Therapy and Pharmacotherapy

    Science.gov (United States)

    Bagby, R Michael; Quilty, Lena C; Segal, Zindel V; McBride, Carolina C; Kennedy, Sidney H; Costa, Paul T

    2008-01-01

    Objective Effective treatments for major depressive disorder exist, yet some patients fail to respond, or achieve only partial response. One approach to optimizing treatment success is to identify which patients are more likely to respond best to which treatments. The objective of this investigation was to determine if patient personality characteristics are predictive of response to either cognitive-behavioural therapy (CBT) or pharmacotherapy (PHT). Method Depressed patients completed the Revised NEO Personality Inventory, which measures the higher-order domain and lower-order facet traits of the Five-Factor Model of Personality, and were randomized to receive either CBT or PHT. Result Four personality traits—the higher-order domain neuroticism and 3 lower-order facet traits: trust, straightforwardness, and tendermindedness—were able to distinguish a differential response rate to CBT, compared with PHT. Conclusion The assessment of patient dimensional personality traits can assist in the selection and optimization of treatment response for depressed patients. PMID:18616856

  1. Molecular targeted therapy in modern oncology: Imaging assessment of treatment response and toxicities

    Energy Technology Data Exchange (ETDEWEB)

    Krajewski, Katherine M.; Braschi-Amirfarzan, Marta; DiPiro, Pamela J.; Jagannathan, Jyothi P.; Shinagare, Atul B. [Dept. of of Imaging, Dana Farber Cancer Institute, Boston (United States)

    2017-01-15

    Oncology is a rapidly evolving field with a shift toward personalized cancer treatment. The use of therapies targeted to the molecular features of individual tumors and the tumor microenvironment has become much more common. In this review, anti-angiogenic and other molecular targeted therapies are discussed, with a focus on typical and atypical response patterns and imaging manifestations of drug toxicities.

  2. Intestinal fibrosis is associated with lack of response to Infliximab therapy in Crohn's disease

    NARCIS (Netherlands)

    de Bruyn, Jessica R.; Becker, Marte A.; Steenkamer, Jessica; Wildenberg, Manon E.; Meijer, Sybren L.; Buskens, Christianne J.; Bemelman, Willem A.; Löwenberg, Mark; Ponsioen, Cyriel Y.; van den Brink, Gijs R.; D'Haens, Geert R.

    2018-01-01

    Overt fibrostenotic disease is a relative contraindication for anti-TNF therapy in Crohn's disease. We hypothesized that subclinical fibrosis may also contribute to an incomplete response to anti-TNF therapy before the onset of symptomatic stenosis. In a previous trial, patients with ileocecal

  3. Ethical Responsibilities: Preparing Students for the Real Art Therapy World

    Science.gov (United States)

    Gussak, David E.; Orr, Penelope

    2005-01-01

    This report addresses several educators' attempts to prepare their students for entering the "real" art therapy world. Two important components necessary to prepare students for entering the professional arenas are introduced: the need to translate theory into practice and the ability to communicate and negotiate with other helping professionals.…

  4. Heterogeneity in response during multisystemic therapy: Exploring subgroups and predictors

    NARCIS (Netherlands)

    Mertens, E.C.A.; Dekovic, M.; Asscher, J.J.; Manders, W.A.

    2017-01-01

    Multiple studies have shown that Multisystemic Therapy (MST) is, at group level, an effective treatment for adolescents showing serious externalizing problem behavior. The current study expands previous research on MST by, first, examining whether subgroups of participants who respond differently to

  5. Heterogeneity in response during Multisystemic Therapy : Exploring subgroups and predictors

    NARCIS (Netherlands)

    Mertens, E.C.A.; Dekovic, M.; Asscher, J.J.; Manders, W.A.

    2017-01-01

    Multiple studies have shown that Multisystemic Therapy (MST) is, at group level, an effective treatment for adolescents showing serious externalizing problem behavior. The current study expands previous research on MST by, first, examining whether subgroups of participants who respond differently to

  6. Dimentions of Counselee Responses over Several Therapy Sessions

    Science.gov (United States)

    Zimmer, Jules M.; And Others

    1972-01-01

    The results of the current study, as well as the Zimmer and Cowles (1972) study using quite different procedures, involved a comparison of client-centered, gestalt, and rational therapies and do not support the conclusion that therapeutic relationships tend to be characteristically the same. Theoretical orientation as operationalized by…

  7. A Commentary on the Social Responsibility of Occupational Therapy Education

    Science.gov (United States)

    Sakellariou, Dikaios; Pollard, Nick

    2013-01-01

    As one of the allied health professions, occupational therapy has adopted a primarily clinical focus on human occupation (or the process of daily life) and this is reflected in education, which has until recently tended to overlook contextual social factors such as poverty, marginalisation, exclusion, unemployment, incarceration and immigration.…

  8. Predicting compliance for mandible advancement splint therapy in 96 obstructive sleep apnea patients.

    Science.gov (United States)

    Ingman, Tuula; Arte, Sirpa; Bachour, Adel; Bäck, Leif; Mäkitie, Antti

    2013-12-01

    The treatment of choice in obstructive sleep apnea (OSA) is continuous positive airway pressure (CPAP). Mandible advancement splint (MAS) offers an option for patients with mild or moderate OSA, who refuse or are unable to tolerate CPAP. The aim of the study was to find predictive factors in OSA for MAS therapy. The study group comprised 96 consecutive OSA patients who were sent for MAS therapy during 2008. Data were collected on the patients' general and dental condition, diagnosis, and treatment for OSA. Panoramic and cephalometric radiographs were analysed. The treatment compliance rate and problems with the use of the MAS were recorded. This rate was 57% and the significant affecting factors were protrusion of the mandible with MAS during the adaptation to the appliance as well as shorter maxillary and mandible lengths. The compliance of the MAS therapy was best in patients with short maxilla and mandible, which should be taken into consideration when planning MAS therapy for OSA patients. Finally, a sleep study should be part of the follow-up in this patient population.

  9. Stereotype confirmation concerns predict dropout from cognitive behavioral therapy for social anxiety disorder.

    Science.gov (United States)

    Johnson, Suzanne; Price, Matthew; Mehta, Natasha; Anderson, Page L

    2014-08-19

    There are high attrition rates observed in efficacy studies for social anxiety disorder, and research has not identified consistent nor theoretically meaningful predictors of dropout. Pre-treatment symptom severity and demographic factors, such as age and gender, are sometimes predictive of dropout. The current study examines a theoretically meaningful predictor of attrition based on experiences associated with social group membership rather than differences between social group categories--fear of confirming stereotypes. This is a secondary data analysis of a randomized controlled trial comparing two cognitive behavioral treatments for social anxiety disorder: virtual reality exposure therapy and exposure group therapy. Participants (N = 74) with a primary diagnosis of social anxiety disorder who were eligible to participate in the parent study and who self-identified as either "African American" (n = 31) or "Caucasian" (n = 43) completed standardized self-report measures of stereotype confirmation concerns (SCC) and social anxiety symptoms as part of a pre-treatment assessment battery. Hierarchical logistic regression showed that greater stereotype confirmation concerns were associated with higher dropout from therapy--race, age, gender, and pre-treatment symptom severity were not. Group treatment also was associated with higher dropout. These findings urge further research on theoretically meaningful predictors of attrition and highlight the importance of addressing cultural variables, such as the experience of stereotype confirmation concerns, during treatment of social anxiety to minimize dropout from therapy.

  10. Cognitive-behavioral therapy for obsessive–compulsive disorder: access to treatment, prediction of long-term outcome with neuroimaging

    Science.gov (United States)

    O’Neill, Joseph; Feusner, Jamie D

    2015-01-01

    This article reviews issues related to a major challenge to the field for obsessive–compulsive disorder (OCD): improving access to cognitive-behavioral therapy (CBT). Patient-related barriers to access include the stigma of OCD and reluctance to take on the demands of CBT. Patient-external factors include the shortage of trained CBT therapists and the high costs of CBT. The second half of the review focuses on one partial, yet plausible aid to improve access – prediction of long-term response to CBT, particularly using neuroimaging methods. Recent pilot data are presented revealing a potential for pretreatment resting-state functional magnetic resonance imaging and magnetic resonance spectroscopy of the brain to forecast OCD symptom severity up to 1 year after completing CBT. PMID:26229514

  11. Does respiratory sinus arrhythmia (RSA) predict anxiety reduction during cognitive behavioral therapy (CBT) for social anxiety disorder (SAD)?

    Science.gov (United States)

    Mathewson, Karen J; Schmidt, Louis A; Miskovic, Vladimir; Santesso, Diane L; Duku, Eric; McCabe, Randi E; Antony, Martin M; Moscovitch, David A

    2013-05-01

    Modifying dysfunctional emotion regulation is an important goal in psychological treatments for social anxiety disorder (SAD). Antecedent-focused strategies learned in cognitive behavioral therapy (CBT), such as cognitive reappraisal, have proven more effective in reducing social anxiety than response-focused strategies, such as expressive suppression. Still, not all patients with SAD respond well to CBT. Medications and physiological factors may also influence the clinical response. The purpose of the present study was to examine the role that these factors play in determining treatment response following CBT for SAD. Using multilevel modeling, we examined associations across four separate laboratory visits between change in self-reported anxiety and indices of reappraisal, suppression, medication status, and resting respiratory sinus arrhythmia (RSA), a proxy measure of self-regulatory capacity, in 23 socially anxious adults during a 12-week program of CBT. Most participants were ultimately classified as responders to CBT (n=15), but in some, anxiety levels remained unchanged (n=8). Medication use explained substantial variance related to individual differences in anxiety among participants. When modeled separately, reappraisal, suppression, and RSA each accounted for significant variance related to anxiety. However, the best-fitting model included reappraisal and RSA. Moreover, RSA reactivity (change in RSA levels over time) was more important for predicting anxiety reduction than were baseline levels of RSA. These findings suggest that reappraisal and parasympathetic responsiveness may be important in reducing anxiety in adults with SAD who respond well to CBT. Copyright © 2013 Elsevier B.V. All rights reserved.

  12. Apoptosis and other immune biomarkers predict influenza vaccine responsiveness

    National Research Council Canada - National Science Library

    Furman, David; Jojic, Vladimir; Kidd, Brian; Shen‐Orr, Shai; Price, Jordan; Jarrell, Justin; Tse, Tiffany; Huang, Huang; Lund, Peder; Maecker, Holden T; Utz, Paul J; Dekker, Cornelia L; Koller, Daphne; Davis, Mark M

    ... (60 to >89 years) as models for strong and weak immune responses, respectively, and assayed their serological responses to influenza strains as well as a wide variety of other parameters, including gene expression...

  13. EEG does not predict response to valproate treatment of aggression in patients with borderline and antisocial personality disorders.

    Science.gov (United States)

    Reeves, Roy R; Struve, Frederick A; Patrick, Gloria

    2003-04-01

    Previous investigations of the role of EEG in predicting response of aggressive patients to valproate therapy have yielded mixed results. In this study of borderline and antisocial personality disorder patients hospitalized with aggressive behavior, EEGs were obtained prior to treatment with valproate. Eight of 22 (36.4%) patients subsequently responsive to valproate had nonepileptiform EEG abnormalities, while 5 of 20 (25%) patients not responsive to valproate had nonepileptiform EEG abnormalities. Although more of the valproate responders than nonresponders had EEG abnormalities, the presence of nonepileptiform EEG abnormalities was not a statistically significant (X2 = 0.213, df = 1, p = 0.64) predictor of valproate response in personality disorder patients with aggression.

  14. Older Persons' Reasoning about Responsibility for Health: Variations and Predictions

    Science.gov (United States)

    Kjellstrom, Sofia; Ross, Sara Nora

    2011-01-01

    With many Western societies structured for adults to live longer and take responsibility for their health, it is valuable to investigate how older persons reason about this demand. Using mixed methods, this pilot studied how older persons reason about responsibility for health and their responsibility as a patient. Interviews with a small Swedish…

  15. Measurement of the Red Blood Cell Distribution Width Improves the Risk Prediction in Cardiac Resynchronization Therapy

    Directory of Open Access Journals (Sweden)

    András Mihály Boros

    2016-01-01

    Full Text Available Objectives. Increases in red blood cell distribution width (RDW and NT-proBNP (N-terminal pro-B-type natriuretic peptide predict the mortality of chronic heart failure patients undergoing cardiac resynchronization therapy (CRT. It was hypothesized that RDW is independent of and possibly even superior to NT-proBNP from the aspect of long-term mortality prediction. Design. The blood counts and serum NT-proBNP levels of 134 patients undergoing CRT were measured. Multivariable Cox regression models were applied and reclassification analyses were performed. Results. After separate adjustment to the basic model of left bundle branch block, beta blocker therapy, and serum creatinine, both the RDW > 13.35% and NT-proBNP > 1975 pg/mL predicted the 5-year mortality (n=57. In the final model including all variables, the RDW [HR = 2.49 (1.27–4.86; p=0.008] remained a significant predictor, whereas the NT-proBNP [HR = 1.18 (0.93–3.51; p=0.07] lost its predictive value. On addition of the RDW measurement, a 64% net reclassification improvement and a 3% integrated discrimination improvement were achieved over the NT-proBNP-adjusted basic model. Conclusions. Increased RDW levels accurately predict the long-term mortality of CRT patients independently of NT-proBNP. Reclassification analysis revealed that the RDW improves the risk stratification and could enhance the optimal patient selection for CRT.

  16. Hepatitis B Virus Infection and Response to Antiretroviral Therapy (ART) in a South African ART Program

    National Research Council Canada - National Science Library

    Christopher J. Hoffmann; Salome Charalambous; Desmond J. Martin; Craig Innes; Gavin J. Churchyard; Richard E. Chaisson; Alison D. Grant; Katherine L. Fielding; Chloe L. Thio

    2008-01-01

    .... We evaluated the impact of chronic hepatitis B on HIV virologic response, changes in CD4 cell count, hepatotoxicity, and mortality among Africans receiving highly active antiretroviral therapy (HAART...

  17. Predictive model for photodynamic therapy with gold nanoparticles as vehicle for the photosensitizer delivery

    Science.gov (United States)

    Salas-García, I.; Fanjul-Vélez, F.; Ortega-Quijano, N.; Arce-Diego, J. L.

    2013-06-01

    Photodynamic Therapy offers multiple advantages to treat nonmelanoma skin cancer compared to conventional treatment techniques such as surgery, radiotherapy or chemotherapy. Among these advantages are particularly relevant its noninvasive nature, the use of non ionizing radiation and its high selectivity. However the therapeutic efficiency of the current clinical protocol is not complete in all the patients and depends on the type of pathology. Emerging strategies to overcome its current shortcomings include the use of nanostructures that can act as carriers for conventional photosensitizers and improve the treatment selectivity and provide a controlled release of the photoactive agent. In this work, a model for photodynamic therapy combined with gold nanocarriers for a photosensitizer commonly used in dermatology is presented and applied to a basal cell carcinoma in order to predict the cytotoxic agent spatial and temporal evolution.

  18. Response to pediatric physical therapy in infants with positional preference and skull deformation.

    Science.gov (United States)

    van Wijk, Renske M; Pelsma, Maaike; Groothuis-Oudshoorn, Catharina G M; IJzerman, Maarten J; van Vlimmeren, Leo A; Boere-Boonekamp, Magda M

    2014-09-01

    Pediatric physical therapy seems to reduce skull deformation in infants with positional preference. However, not all infants show improvement. The study objective was to determine which infant and parent characteristics were related to responses to pediatric physical therapy in infants who were 2 to 4 months old and had positional preference, skull deformation, or both. This was a prospective cohort study. Infants who were 2 to 4 months old and had positional preference, skull deformation, or both were recruited by pediatric physical therapists at the start of pediatric physical therapy. The primary outcome was a good response or a poor response (moderate or severe skull deformation) at 4.5 to 6.5 months of age. Potential predictors for responses to pediatric physical therapy were assessed at baseline with questionnaires, plagiocephalometry, and the Alberta Infant Motor Scale. Univariate and multiple logistic regression analyses with a stepwise backward elimination method were performed. A total of 657 infants participated in the study. At follow-up, 364 infants (55.4%) showed a good response to therapy, and 293 infants (44.6%) showed a poor response. Multiple logistic regression analysis resulted in the identification of several significant predictors for a poor response to pediatric physical therapy at baseline: starting therapy after 3 months of age (adjusted odds ratio [aOR]=1.50, 95% confidence interval [95% CI]=1.04-2.17), skull deformation (plagiocephaly [aOR=2.64, 95% CI=1.67-4.17] or brachycephaly [aOR=3.07, 95% CI=2.09-4.52]), and a low parental satisfaction score (aOR=2.64, 95% CI=1.67-4.17). A low parental satisfaction score indicates low parental satisfaction with the infant's head shape. Information about pediatric physical therapy was collected retrospectively and included general therapy characteristics. Because data were collected retrospectively, no adjustment in therapy for individual participants could be made. Several predictors for responses

  19. Response to the treatment immediately before nivolumab monotherapy may predict clinical response to nivolumab in patients with non-small cell lung cancer.

    Science.gov (United States)

    Kobayashi, Haruki; Omori, Shota; Nakashima, Kazuhisa; Wakuda, Kazushige; Ono, Akira; Kenmotsu, Hirotsugu; Naito, Tateaki; Murakami, Haruyasu; Endo, Masahiro; Takahashi, Toshiaki

    2017-08-01

    Currently, no markers predictive of response to nivolumab monotherapy in patients with advanced non-small cell lung cancer (NSCLC) are currently recognized in Japan. The present study was undertaken to identify such markers. Medical records of 50 patients with advanced NSCLC and treated with nivolumab monotherapy at Shizuoka Cancer Center between December 2015 and April 2016 were retrospectively reviewed. The parameters studied were age, sex, Eastern Cooperative Oncology Group performance status, smoking history, histological diagnosis, epidermal growth factor receptor or anaplastic lymphoma kinase status, therapeutic line of nivolumab, efficacy of treatment immediately before nivolumab monotherapy, and time since previous therapy. The objective response rate to nivolumab monotherapy was 18% [95% confidence interval (CI) 10-31]. Multivariate logistic regression identified "squamous histology" [odds ratio (OR) 0.00054; 95% CI 0-0.27] and "response to the treatment immediately before nivolumab monotherapy" (OR 0.0011; 95% CI 0-0.092) as independently associated with response to nivolumab monotherapy. "Response to the treatment immediately before nivolumab monotherapy" might be a predictive marker of response to nivolumab in patients with advanced NSCLC.

  20. Determination of breast cancer response to bevacizumab therapy using contrast-enhanced ultrasound and artificial neural networks.

    Science.gov (United States)

    Hoyt, Kenneth; Warram, Jason M; Umphrey, Heidi; Belt, Lin; Lockhart, Mark E; Robbin, Michelle L; Zinn, Kurt R

    2010-04-01

    The purpose of this study was to evaluate contrast-enhanced ultrasound and neural network data classification for determining the breast cancer response to bevacizumab therapy in a murine model. An ultrasound scanner operating in the harmonic mode was used to measure ultrasound contrast agent (UCA) time-intensity curves in vivo. Twenty-five nude athymic mice with orthotopic breast cancers received a 30-microL tail vein bolus of a perflutren microsphere UCA, and baseline tumor imaging was performed using microbubble destruction-replenishment techniques. Subsequently, 15 animals received a 0.2-mg injection of bevacizumab, whereas 10 control animals received an equivalent dose of saline. Animals were reimaged on days 1, 2, 3, and 6 before euthanasia. Histologic assessment of excised tumor sections was performed. Time-intensity curve analysis for a given region of interest was conducted using customized software. Tumor perfusion metrics on days 1, 2, 3, and 6 were modeled using neural network data classification schemes (60% learning and 40% testing) to predict the breast cancer response to therapy. The breast cancer response to a single dose of bevacizumab in a murine model was immediate and transient. Permutations of input to the neural network data classification scheme revealed that tumor perfusion data within 3 days of bevacizumab dosing was sufficient to minimize the prediction error to 10%, whereas measurements of physical tumor size alone did not appear adequate to assess the therapeutic response. Contrast-enhanced ultrasound may be a useful tool for determining the response to bevacizumab therapy and monitoring the subsequent restoration of blood flow to breast cancer.

  1. Acute phase cognitive therapy for recurrent major depressive disorder: who drops out and how much do patient skills influence response?

    Science.gov (United States)

    Jarrett, Robin B; Minhajuddin, Abu; Kangas, Julie L; Friedman, Edward S; Callan, Judith A; Thase, Michael E

    2013-05-01

    The aims were to predict cognitive therapy (CT) noncompletion and to determine, relative to other putative predictors, the extent to which the patient skills in CT for recurrent major depressive disorder predicted response in a large, two-site trial. Among 523 outpatients aged 18e70, exposed to 12e14 weeks of CT, 21.6% dropped out. Of the 410 completers, 26.1% did not respond. To predict these outcomes, we conducted logistic regression analyses of demographics, pre-treatment illness characteristics and psychosocial measures, and midtreatment therapeutic alliance. The 17-item Hamilton Rating Scale for Depression (HRSD17) scores at entry predicted dropout and nonresponse. Patients working for pay, of non-Hispanic white race, who were older, or had more education were significantly more likely to complete. Controlling for HRSD17, significant predictors of nonresponse included: lower scores on the Skills of Cognitive Therapy-Observer Version (SoCT-O), not working for pay, history of only two depressive episodes, greater pre-treatment social impairment. Midphase symptom reduction was a strong predictor of final outcome. These prognostic indicators forecast which patients tend to be optimal candidates for standard CT, as well as which patients may benefit from changes in therapy, its focus, or from alternate modalities of treatment. Pending replication, the findings underscore the importance of promoting patients’ understanding and use of CT skills, as well as reducing depressive symptoms early. Future research may determine the extent to which these findings generalize to other therapies, providers who vary in competency, and patients with other depressive subtypes or disorders.

  2. Evaluating the molecule-based prediction of clinical drug responses in cancer.

    Science.gov (United States)

    Ding, Zijian; Zu, Songpeng; Gu, Jin

    2016-10-01

    Molecule-based prediction of drug response is one major task of precision oncology. Recently, large-scale cancer genomic studies, such as The Cancer Genome Atlas (TCGA), provide the opportunity to evaluate the predictive utility of molecular data for clinical drug responses in multiple cancer types. Here, we first curated the drug treatment information from TCGA. Four chemotherapeutic drugs had more than 180 clinical response records. Then, we developed a computational framework to evaluate the molecule based predictions of clinical responses of the four drugs and to identify the corresponding molecular signatures. Results show that mRNA or miRNA expressions can predict drug responses significantly better than random classifiers in specific cancer types. A few signature genes are involved in drug response related pathways, such as DDB1 in DNA repair pathway and DLL4 in Notch signaling pathway. Finally, we applied the framework to predict responses across multiple cancer types and found that the prediction performances get improved for cisplatin based on miRNA expressions. Integrative analysis of clinical drug response data and molecular data offers opportunities for discovering predictive markers in cancer. This study provides a starting point to objectively evaluate the molecule-based predictions of clinical drug responses. jgu@tsinghua.edu.cn Supplementary data are available at Bioinformatics online. © The Author 2016. Published by Oxford University Press. All rights reserved. For Permissions, please e-mail: journals.permissions@oup.com.

  3. PREDICTING MICROEVOLUTIONARY RESPONSES TO DIRECTIONAL SELECTION ON HERITABLE VARIATION.

    Science.gov (United States)

    Grant, Peter R; Grant, B Rosemary

    1995-04-01

    Microevolution of quantitative traits in the wild can be predicted from a knowledge of selection and genetic parameters. Testing the predictions requires measurement of the offspring of the selected group, a requirement that is difficult to meet. We present the results of a study of Darwin's finches on the Galápagos island of Daphne Major where this requirement is met. The study demonstrates microevolutionary consequences of natural selection. © 1995 The Society for the Study of Evolution.

  4. The next generation of metastatic melanoma: uncovering the genetic variants for anti-BRAF therapy response.

    Science.gov (United States)

    Pinto, Rosamaria; De Summa, Simona; Strippoli, Sabino; Pilato, Brunella; Azzariti, Amalia; Guida, Gabriella; Guida, Michele; Tommasi, Stefania

    2016-05-03

    Metastatic melanoma (MM) is a highly aggressive cancer with a median overall survival of 6-9 months, notwithstanding the numerous efforts in development of new therapeutic approaches. To this aim we tested the clinical applicability of the Ion Torrent Personal Genome Machine to simultaneously screen MM patients in order to individuate new or already known SNPs and mutations able to predict the duration of response to BRAF inhibitors. An Ampliseq Custom Panel, including 11 crucial full length genes involved in melanoma carcinogenesis and therapy response pathways, was created and used to analyze 25 MM patients. We reported BRAFV600 and NRASQ61 mutations in 68% and 24% of samples, respectively. Moreover, we more frequently identified the following alterations related to BRAF status: PIK3CAI391M (44%) and KITD737N (36%) mutations, CTLA4T17A (52%), MC1RV60L (32%) and MITFS473A (60%) polymorphisms. Considering the progression free survival (PFS), statistical analyses showed that BRAFV600 patients without any of these more frequent alterations had a higher median PFS. Protein structure changes seem to be due to these variants by in silico analysis. In conclusion, a Next-Generation Sequencing approach with custom panel may provide new information to evaluate tumor-specific therapeutic susceptibility and individual prognosis to improve the care of MM patients.

  5. Predicting uptake of continuous positive airway pressure (CPAP) therapy in obstructive sleep apnoea (OSA)

    DEFF Research Database (Denmark)

    Skinner, Timothy; McNeil, Lindsay; Olaithe, Michelle

    2013-01-01

    Purpose: Obstructive sleep apnoea (OSA) is a common disorder, for which continuous positive airway pressure (CPAP) therapy is a standard treatment. Despite its well-established efficacy, many patients choose not to initiate CPAP treatment. The present study investigated the degree to which...... decision to proceed with a trial of CPAP. Results: The participants were most likely to attribute their OSA to unchangeable and psychological factors. For those with moderate OSA (AHI, 15 to 30) IPQ-R illness consequence was predictive of decision to initiate CPAP (p = 0.002). For severe OSA (AHI >30) age...

  6. Predictability of the individual clinical outcome of extracorporeal shock wave therapy for cellulite

    Directory of Open Access Journals (Sweden)

    Schlaudraff KU

    2014-05-01

    Full Text Available Kai-Uwe Schlaudraff,1 Maren C Kiessling,2 Nikolaus BM Császár,2 Christoph Schmitz21Concept Clinic, Geneva, Switzerland; 2Department of Anatomy II, Ludwig-Maximilians-University of Munich, Munich, GermanyBackground: Extracorporeal shock wave therapy has been successfully introduced for the treatment of cellulite in recent years. However, it is still unknown whether the individual clinical outcome of cellulite treatment with extracorporeal shock wave therapy can be predicted by the patient's individual cellulite grade at baseline, individual patient age, body mass index (BMI, weight, and/or height.Methods: Fourteen Caucasian females with cellulite were enrolled in a prospective, single-center, randomized, open-label Phase II study. The mean (± standard error of the mean cellulite grade at baseline was 2.5±0.09 and mean BMI was 22.8±1.17. All patients were treated with radial extracorporeal shock waves using the Swiss DolorClast® device (Electro Medical Systems, S.A., Nyon, Switzerland. Patients were treated unilaterally with 2 weekly treatments for 4 weeks on a randomly selected side (left or right, totaling eight treatments on the selected side. Treatment was performed at 3.5–4.0 bar, with 15,000 impulses per session applied at 15 Hz. Impulses were homogeneously distributed over the posterior thigh and buttock area (resulting in 7,500 impulses per area. Treatment success was evaluated after the last treatment and 4 weeks later by clinical examination, photographic documentation, contact thermography, and patient satisfaction questionnaires.Results: The mean cellulite grade improved from 2.5±0.09 at baseline to 1.57±0.18 after the last treatment (ie, mean δ-1 was 0.93 cellulite grades and 1.68±0.16 at follow-up (ie, mean δ-2 was 0.82 cellulite grades. Compared with baseline, no patient's condition worsened, the treatment was well tolerated, and no unwanted side effects were observed. No statistically significant (ie, P<0

  7. The orthodontist’s civil responsibility post-orthodontic therapy

    OpenAIRE

    Mayury Kuramae; Heloisa Cristina Valdrighi; Silvia Amélia Scudeler Vedovello; Mário Vedovello Filho; Maurício Garcia Barroso; Viviane Vaz

    2008-01-01

    Objective: The aim of this work was to investigate what the orthodontist’s difficulties are, analyzing whether the adopted procedures are able to satisfy the complaints of individuals, who already concluded orthodontic therapy, according to the determinations of the civil code and the Costumer’s Defense Code, as well as the relationship between patient and professional. Methods: A questionnaire was sent by postal service to all the odonthology specialists inrolled in the CRO/RJ amounting to 9...

  8. Childhood trauma predicts antidepressant response in adults with major depression: data from the randomized international study to predict optimized treatment for depression

    Science.gov (United States)

    Williams, L M; Debattista, C; Duchemin, A-M; Schatzberg, A F; Nemeroff, C B

    2016-01-01

    Few reliable predictors indicate which depressed individuals respond to antidepressants. Several studies suggest that a history of early-life trauma predicts poorer response to antidepressant therapy but results are variable and limited in adults. The major goal of the present study was to evaluate the role of early-life trauma in predicting acute response outcomes to antidepressants in a large sample of well-characterized patients with major depressive disorder (MDD). The international Study to Predict Optimized Treatment for Depression (iSPOT-D) is a randomized clinical trial with enrollment from December 2008 to January 2012 at eight academic and nine private clinical settings in five countries. Patients (n=1008) meeting DSM-IV criteria for MDD and 336 matched healthy controls comprised the study sample. Six participants withdrew due to serious adverse events. Randomization was to 8 weeks of treatment with escitalopram, sertraline or venlafaxine with dosage adjusted by the participant's treating clinician per routine clinical practice. Exposure to 18 types of traumatic events before the age of 18 was assessed using the Early-Life Stress Questionnaire. Impact of early-life stressors—overall trauma ‘load' and specific type of abuse—on treatment outcomes measures: response: (⩾50% improvement on the 17-item Hamilton Rating Scale for Depression, HRSD17 or on the 16-item Quick Inventory of Depressive Symptomatology—Self-Rated, QIDS_SR16) and remission (score ⩽7 on the HRSD17 and ⩽5 on the QIDS_SR16). Trauma prevalence in MDD was compared with controls. Depressed participants were significantly more likely to report early-life stress than controls; 62.5% of MDD participants reported more than two traumatic events compared with 28.4% of controls. The higher rate of early-life trauma was most apparent for experiences of interpersonal violation (emotional, sexual and physical abuses). Abuse and notably abuse occurring at ⩽7 years of age predicted poorer

  9. Predicting binaural responses from monaural responses in the gerbil medial superior olive.

    Science.gov (United States)

    Plauška, Andrius; Borst, J Gerard; van der Heijden, Marcel

    2016-06-01

    Accurate sound source localization of low-frequency sounds in the horizontal plane depends critically on the comparison of arrival times at both ears. A specialized brainstem circuit containing the principal neurons of the medial superior olive (MSO) is dedicated to this comparison. MSO neurons are innervated by segregated inputs from both ears. The coincident arrival of excitatory inputs from both ears is thought to trigger action potentials, with differences in internal delays creating a unique sensitivity to interaural time differences (ITDs) for each cell. How the inputs from both ears are integrated by the MSO neurons is still debated. Using juxtacellular recordings, we tested to what extent MSO neurons from anesthetized Mongolian gerbils function as simple cross-correlators of their bilateral inputs. From the measured subthreshold responses to monaural wideband stimuli we predicted the rate-ITD functions obtained from the same MSO neuron, which have a damped oscillatory shape. The rate of the oscillations and the position of the peaks and troughs were accurately predicted. The amplitude ratio between dominant and secondary peaks of the rate-ITD function, captured in the width of its envelope, was not always exactly reproduced. This minor imperfection pointed to the methodological limitation of using a linear representation of the monaural inputs, which disregards any temporal sharpening occurring in the cochlear nucleus. The successful prediction of the major aspects of rate-ITD curves supports a simple scheme in which the ITD sensitivity of MSO neurons is realized by the coincidence detection of excitatory monaural inputs. Copyright © 2016 the American Physiological Society.

  10. The 20th anniversary of interleukin-2 therapy: bimodal role explaining longstanding random induction of complete clinical responses

    Science.gov (United States)

    Coventry, Brendon J; Ashdown, Martin L

    2012-01-01

    Background This year marks the twentieth anniversary of the approval by the US Food and Drug Administration of interleukin-2 (IL2) for use in cancer therapy, initially for renal cell carcinoma and later for melanoma. IL2 therapy for cancer has stood the test of time, with continued widespread use in Europe, parts of Asia, and the US. Clinical complete responses are variably reported at 5%–20% for advanced malignant melanoma and renal cell carcinoma, with strong durable responses and sustained long-term 5–10-year survival being typical if complete responses are generated. Methods The literature was reviewed for the actions and clinical effects of IL2 on subsets of T cells. The influence of IL2 on clinical efficacy was also sought. Results The review revealed that IL2 is capable of stimulating different populations of T cells in humans to induce either T effector or T regulatory responses. This apparent “functional paradox” has confounded a clear understanding of the mechanisms behind the clinical effects that are observed during and following administration of IL2 therapy. An average complete response rate of around 7% in small and large clinical trials using IL2 for advanced renal cell carcinoma and malignant melanoma has been shown from a recent review of the literature. Conclusion This review considers the published literature concerning the actions and emerging clinical effects of IL2 therapy, spanning its 20-year period in clinical use. It further details some of the recently described “bimodal” effects of IL2 to explain the apparent functional paradox, and how IL2 might be harnessed to emerge rapidly as a much more effective and predictable clinical agent in the near future. PMID:22904643

  11. Mindfulness predicts relapse/recurrence in major depressive disorder after mindfulness-based cognitive therapy.

    Science.gov (United States)

    Michalak, Johannes; Heidenreich, Thomas; Meibert, Petra; Schulte, Dietmar

    2008-08-01

    Empirical evidence for the effectiveness of mindfulness-based cognitive therapy (MBCT) is encouraging. However, data concerning the role of mindfulness in its relapse preventive effect are lacking. In our study, 25 formerly depressed patients received MBCT. Mindfulness was assessed before and immediately after MBCT using the Mindful Attention and Awareness Scale. Mindfulness significantly increased during MBCT, and posttreatment levels of mindfulness predicted the risk of relapse/recurrence to major depressive disorder in the 12-month follow-up period. Mindfulness predicted the risk of relapse/recurrence after controlling for numbers of previous episodes and residual depressive symptoms. The results provide preliminary evidence for the notion that mindfulness is an important factor in relapse prevention in major depression.

  12. Predictive value of NGAL for use of renal replacement therapy in patients with severe sepsis

    DEFF Research Database (Denmark)

    Hjortrup, P B; Haase, N; Treschow, F

    2015-01-01

    BACKGROUND: The predictive value of plasma and urine neutrophil gelatinase-associated lipocalin (NGAL) for use of renal replacement therapy (RRT) and acute kidney injury (AKI) is not established in patients with severe sepsis. METHODS: This was a prospective observational study in three general...... intensive care units (ICUs) in adult ICU patients with severe sepsis needing fluid resuscitation and a sub-study of the 6S trial. Plasma and urine were sampled at baseline and NGAL was measured using particle-enhanced turbidimetric immunoassay (The NGAL Test). Outcome measures were use of RRT in ICU......%) had RRT in the ICU, 91 patients had AKI at enrollment; of the remaining 131 patients 24% developed AKI during the first 48 h, and 55% had died at 90 days. Areas under receiver-operating characteristics curve (AuROC) for predicting use of RRT in ICU were 0.70 (95% confidence interval 0.61-0.78) and 0...

  13. DNA Repair Biomarkers Predict Response to Neoadjuvant Chemoradiotherapy in Esophageal Cancer

    Energy Technology Data Exchange (ETDEWEB)

    Alexander, Brian M., E-mail: bmalexander@lroc.harvard.edu [Department of Radiation Oncology, Dana-Farber/Brigham and Women' s Cancer Center, Boston, Massachusetts (United States); Wang Xiaozhe [On-Q-ity, Inc., Waltham, Massachusetts (United States); Niemierko, Andrzej [Department of Radiation Oncology, Massachusetts General Hospital, Boston, Massachusetts (United States); Weaver, David T. [On-Q-ity, Inc., Waltham, Massachusetts (United States); Mak, Raymond H. [Department of Radiation Oncology, Dana-Farber/Brigham and Women' s Cancer Center, Boston, Massachusetts (United States); Roof, Kevin S. [Southeast Radiation Oncology, Charlotte, North Carolina (United States); Fidias, Panagiotis [Department of Medicine, Massachusetts General Hospital, Boston, Massachusetts (United States); Wain, John [Department of Surgery, Massachusetts General Hospital, Boston, Massachusetts (United States); Choi, Noah C. [Department of Radiation Oncology, Massachusetts General Hospital, Boston, Massachusetts (United States)

    2012-05-01

    Purpose: The addition of neoadjuvant chemoradiotherapy prior to surgical resection for esophageal cancer has improved clinical outcomes in some trials. Pathologic complete response (pCR) following neoadjuvant therapy is associated with better clinical outcome in these patients, but only 22% to 40% of patients achieve pCR. Because both chemotherapy and radiotherapy act by inducing DNA damage, we analyzed proteins selected from multiple DNA repair pathways, using quantitative immunohistochemistry coupled with a digital pathology platform, as possible biomarkers of treatment response and clinical outcome. Methods and Materials: We identified 79 patients diagnosed with esophageal cancer between October 1994 and September 2002, with biopsy tissue available, who underwent neoadjuvant chemoradiotherapy prior to surgery at the Massachusetts General Hospital and used their archived, formalin-fixed, paraffin-embedded biopsy samples to create tissue microarrays (TMA). TMA sections were stained using antibodies against proteins in various DNA repair pathways including XPF, FANCD2, PAR, MLH1, PARP1, and phosphorylated MAPKAP kinase 2 (pMK2). Stained TMA slides were evaluated using machine-based image analysis, and scoring incorporated both the intensity and the quantity of positive tumor nuclei. Biomarker scores and clinical data were assessed for correlations with clinical outcome. Results: Higher scores for MLH1 (p = 0.018) and lower scores for FANCD2 (p = 0.037) were associated with pathologic response to neoadjuvant chemoradiation on multivariable analysis. Staining of MLH1, PARP1, XPF, and PAR was associated with recurrence-free survival, and staining of PARP1 and FANCD2 was associated with overall survival on multivariable analysis. Conclusions: DNA repair proteins analyzed by immunohistochemistry may be useful as predictive markers for response to neoadjuvant chemoradiotherapy in patients with esophageal cancer. These results are hypothesis generating and need

  14. Implicit Learning Abilities Predict Treatment Response in Autism Spectrum Disorders

    Science.gov (United States)

    2015-09-01

    project. The first is to individual differences in implicit learning abilities using behavioral methods in 1) high and low cognitively able children...play interaction. After three months of therapy , the child will complete the same behavioral and social communication skills procedures. We will... behavior among FTO genotypes in pre- obese children 1 R21 MH103650-01 (Broft PI) (Casey WCMC PI) 4/1/2014-5/31/20 NIMH 1.2 CM Impact of negative affect

  15. Random Forests to Predict Rectal Toxicity Following Prostate Cancer Radiation Therapy

    Energy Technology Data Exchange (ETDEWEB)

    Ospina, Juan D. [LTSI, Université de Rennes 1, Rennes (France); INSERM, U1099, Rennes (France); Escuela de Estadística, Universidad Nacional de Colombia Sede Medellín, Medellín (Colombia); Zhu, Jian [LTSI, Université de Rennes 1, Rennes (France); Laboratory of Image Science and Technology, Southeast University, Nanjing (China); Department of Radiation Physics, Shandong Cancer Hospital and Institute, Jinan (China); Centre de Recherche en Information Biomédical Sino-Français, Rennes (France); Chira, Ciprian [Département de Radiothérapie, Centre Eugène Marquis, Rennes (France); Bossi, Alberto [Département de Radiothérapie, Institut Gustave-Roussy, Villejuif (France); Delobel, Jean B. [Département de Radiothérapie, Centre Eugène Marquis, Rennes (France); Beckendorf, Véronique [Département de Radiothérapie, Centre Alexis Vautrin, Nancy (France); Dubray, Bernard [Département de Radiothérapie, CRLCC Henri Becquerel, Rouen (France); Lagrange, Jean-Léon [Département de Radiothérapie, Hôpital Henri Mondor, Créteil (France); Correa, Juan C. [Escuela de Estadística, Universidad Nacional de Colombia Sede Medellín, Medellín (Colombia); and others

    2014-08-01

    Purpose: To propose a random forest normal tissue complication probability (RF-NTCP) model to predict late rectal toxicity following prostate cancer radiation therapy, and to compare its performance to that of classic NTCP models. Methods and Materials: Clinical data and dose-volume histograms (DVH) were collected from 261 patients who received 3-dimensional conformal radiation therapy for prostate cancer with at least 5 years of follow-up. The series was split 1000 times into training and validation cohorts. A RF was trained to predict the risk of 5-year overall rectal toxicity and bleeding. Parameters of the Lyman-Kutcher-Burman (LKB) model were identified and a logistic regression model was fit. The performance of all the models was assessed by computing the area under the receiving operating characteristic curve (AUC). Results: The 5-year grade ≥2 overall rectal toxicity and grade ≥1 and grade ≥2 rectal bleeding rates were 16%, 25%, and 10%, respectively. Predictive capabilities were obtained using the RF-NTCP model for all 3 toxicity endpoints, including both the training and validation cohorts. The age and use of anticoagulants were found to be predictors of rectal bleeding. The AUC for RF-NTCP ranged from 0.66 to 0.76, depending on the toxicity endpoint. The AUC values for the LKB-NTCP were statistically significantly inferior, ranging from 0.62 to 0.69. Conclusions: The RF-NTCP model may be a useful new tool i