tbuckley/cabot-search huggingface dataset:
Augmented Berlin-Frankfurt-Munster therapy abrogates the adverse prognostic significance of slow early response to induction chemotherapy for children and adolescents with acute lymphoblastic leukemia and unfavorable presenting features: a report from the Children's Cancer Group.
Authors: J Nachman, H N Sather, P S Gaynon, J N Lukens, L Wolff, M E Trigg
Journal: Journal of Clinical Oncology (1997)

PURPOSE Compared with previous Children's Cancer Group (CCG) acute lymphoblastic leukemia (ALL) trials, therapy based on the Berlin-Frankfurt-Munster (BFM) 76 trial has effected an improvement in event-free survival (EFS). In an attempt to improve EFS further, CCG investigators formulated an augmented BFM (A-BFM) regimen that provides prolonged, intensified postinduction chemotherapy relative to the CCG-modified BFM regimen. PATIENTS AND METHODS We tested A-BFM in 101 patients with ALL and unfavorable presenting features that showed slow early response (SER) to induction therapy who attained remission on day 28. Their outcome was compared with that of 251 concurrent patients with unfavorable presenting features, a rapid early response to therapy (RER), and remission by day 28, treated with CCG-BFM with or without cranial radiation (CRT). RESULTS The 4-year EFS rate from the end of induction for SER patients treated with A-BFM was 70.8% +/- 4.6%. Seventeen patients remain in continuous remission beyond 5 years. Vincristine (VCR) neurotoxicity developed in 50% of patients, but was rarely debilitating. Allergies to Escherichia coli L-asparaginase (L-ASP) occurred in 35% of patients. Avascular necrosis of bone (AVN) developed in 9% of patients. In comparison, a concurrent RER group treated with standard BFM +/- CRT had a 4-year EFS rate of 73.1% +/- 4.6%. CONCLUSION The toxicity of A-BFM is significant, but acceptable. Compared with historical control SER patients treated with CCG-modified BFM, A-BFM therapy appears to produce a significant improvement in EFS. This is the first study to show that intensive chemotherapy, as given in the A-BFM regimen, can abrogate the adverse prognostic significance of SER.
MAVERICC: A randomized phase II study of mFOLFOX6-bevacizumab (BV) versus FOLFIRI-BV with prospective biomarker stratification in previously untreated metastatic colorectal cancer (mCRC).
Authors: Sachdev P. Thomas, Suprith Badarinath, Richard H. Greenberg, Sang Y. Huh, Kulumani M Sivarajan, Shibao Feng, Stefan Scherer, Christine Litz Curry, Christiane Langer, Heinz-Josef Lenz
Journal: Journal of Clinical Oncology (2012)

TPS3635^ Background: The identification of prognostic and predictive biomarkers could significantly improve the risk-benefit ratio and cost-effectiveness of 1st-line mCRC regimens. This is the first prospective study of tumoral ERCC1 (chemo-resistance marker to platinum compounds) and plasma VEGF-A as potential biomarkers for oxaliplatin- and BV-containing regimens, respectively, in an effort to further define the optimal chemotherapy backbone with biologic therapies, including BV, for mCRC. Methods: In this randomized, open-label, global, phase II study, patients (N=360) with histologically or cytologically confirmed CRC and ≥1 measurable metastatic lesion are stratified at screening by tumoral ERCC1 mRNA expression (high vs low, cutoff of 1.7 [ERCC1/β-actin mRNA]). Eligibility criteria include completion of adjuvant therapy &gt;12 months before screening and an ECOG performance status ≤1. Blood samples are collected to quantify plasma VEGF-A levels. Patients within each ERCC1 stratification group are randomized 1:1 to mFOLFOX6-BV or FOLFIRI-BV administered in 2-week cycles. BV will be given at a dose of 5 mg/kg IV q2w. Patients will remain on study treatment until disease progression (PD) or unacceptable toxicity. If oxaliplatin or irinotecan need to be discontinued, BV and 5-fluorouracil or capecitabine are to be continued until PD. The primary objectives are: 1) to assess ERCC1 and VEGF-A as biomarkers of progression-free survival (PFS) for oxaliplatin- and BV-containing regimens in 1st-line mCRC, and 2) within ERCC1 high patients, to test whether FOLFIRI-BV is associated with a prolonged 1st-line PFS compared to mFOLFOX6-BV. Secondary objectives include assessing the impact of these markers on overall survival, objective response, hepatic metastases resection, and safety. Exploratory endpoints include correlative analyses with additional tumor tissue, blood, and SNP markers. The first patient was enrolled in August 2011. An interim biomarker distribution assessment of the first 100 patients is planned, and the evaluation of the primary endpoints is estimated for early 2015. Clinicaltrials.gov: NCT01374425.
Can we use HCC risk scores to individualize surveillance in chronic hepatitis B infection?
Authors: Vincent Wai-Sun Wong, Harry L.A. Janssen
Journal: Journal of Hepatology (2015)

Chronic hepatitis B is one of the leading causes of hepatocellular carcinoma (HCC) worldwide. Accurate prediction of HCC risk is important for decisions on antiviral therapy and HCC surveillance. In the last few years, a number of Asian groups have derived and validated several HCC risk scores based on well-known risk factors such as cirrhosis, age, male sex and high viral load. Overall, these scores have high negative predictive values of over 95% in excluding HCC development in 3 to 10 years. The REACH-B score was derived from a community cohort of non-cirrhotic patients and is better applied in the primary care setting. In contrast, the GAG-HCC and CU-HCC scores were derived from hospital cohorts and include cirrhosis as a major integral component. While the latter scores may be more applicable to patients at specialist clinics, the diagnosis of cirrhosis based on routine imaging and clinical parameters can be inaccurate. To this end, recent developments in non-invasive tests of liver fibrosis may further refine the risk prediction. The application of HCC risk scores in patients on antiviral therapy and in other ethnic groups should be evaluated in future studies.
Thinking Forward: Future-oriented Thinking among Patients with Tobacco-associated Thoracic Diseases and Their Surrogates
Authors: Joanna L. Hart, Emily Pflug, Vanessa Madden, Scott D. Halpern
Journal: American Journal of Respiratory and Critical Care Medicine (2015)

Rationale: The goal of shared decision making is to match patient preferences, including evaluation of potential future outcomes, with available management options. Yet, it is unknown how patients with smoking-related thoracic diseases or their surrogates display future-oriented thinking.Objectives: To document prevalent themes in patients’ and potential surrogate decision makers’ future-oriented thinking when facing preference-sensitive choices.Methods: We conducted 44 scenario-based semistructured interviews among a diverse group of outpatients with smoking-associated thoracic diseases and potential surrogates for whom one of three preference-sensitive decisions would be medically relevant. Using content analysis, we documented prevalent themes to understand how these individuals display future-oriented thinking.Measurements and Main Results: Patients and potential surrogates generally expressed expectations for future outcomes but also acknowledged their limitations in doing so. When thinking about potential outcomes, decision makers relied on past experiences, including those only loosely related; perceived familiarity with treatment options; and spirituality. The content of these expectations included effects on family, emotional predictions, and prognostication. For surrogates, a tension existed between hope-based and fact-based expectations.Conclusions: Patients and surrogates may struggle to generate expectations, and these future-oriented thoughts may be based on loosely related past experiences or unrealistic optimism. These tendencies may lead to errors, preventing selection of treatments that promote true preferences. Clinicians should explore how decision makers engage in future-oriented thinking and what their expectations are as a component of the shared decision-making process. Future research should evaluate whether targeted guidance in future-oriented thinking may improve outcomes important to patients.
Two psychiatrists who took speaker fees from drug firm resign from Texan hospital
Authors: O. Dyer
Journal: BMJ (2015)

Two psychiatrists have abruptly resigned from a Texas state hospital after learning that they faced disciplinary action for accepting hundreds of thousands of dollars from AstraZeneca while promoting the company’s drug Seroquel XR (extended release quetiapine fumarate) to state officials.

Anthony Claxton, clinical director of Terrell State Hospital, is accused of receiving over $231 000 (£153 000; €207 000) in payment for speaking and consulting services on at least 166 occasions. Lisa Perdue, a psychiatrist at Terrell, allegedly received over $615 000 for similar services performed on at least 460 occasions from 2005 to 2013.

A letter from the Department of State Health Services informed Claxton: “You admitted in sworn testimony that you understood you were being approached by AstraZeneca to promote Seroquel to other state doctors because you are a state doctor …
A novel mutation in the L12 domain of keratin 1 is associated with mild epidermolytic ichthyosis
Authors: M.C. Bolling, R.S. Bladergroen, M.A.M. Van Steensel, M. Willemsen, M.F. Jonkman, M. Van Geel
Journal: British Journal of Dermatology (2010)

Background Epidermolytic ichthyosis (EI), previously termed bullous congenital ichthyosiform erythroderma or epidermolytic hyperkeratosis, is a clinically heterogeneous genodermatosis caused by mutations in the genes encoding the suprabasal keratins 1 and 10. Classical EI is clinically characterized by severe neonatal erythroderma, blistering and fragile skin in infancy, quickly subsiding with subsequent development of generalized scaling hyperkeratosis. We report three Dutch families with palmoplantar keratoderma and mild blistering, but without neonatal erythroderma and generalized scaling. A novel heterozygous missense mutation in the linker L12 domain of KRT1:c.1019A>G, p.Asp340Gly was found associated with this phenotype in these families. Objectives To investigate the effects of the novel KRT1:p.Asp340Gly and the one other previously reported KRT1:p.Asp340Val mutations on keratinocyte cytoskeleton formation and stress resistance. Methods Wild‐type and mutant pEGFP‐KRT1 fusion constructs were transfected into HaCaT cells and exposed to hypo‐osmotic shock. Haplotyping and genealogical studies were performed to investigate the possibility of a common founder for p.Asp340Gly. Results Cells transfected with either one of the keratin 1 L12 domain mutations showed significantly increased tonofilament aggregation. The haplotype around the KRT1 gene was shared in all affected family members of two families and a common founder was traced. Conclusions Our study supports the pathogenicity of the keratin 1 L12 domain mutations in vitro. These mutations are associated with a milder EI phenotype with pronounced palmoplantar keratoderma, and without neonatal erythroderma and scaling. The KRT1:p.Asp340Gly mutation in the Dutch families is likely to have arisen from a common founder.
Regular and moderate exercise prevents airway remodeling in a murine model of chronic allergic asthma
Authors: Cynthia Samary, Carla Araujo, Isabela Guimaraes, Johnatas Silva, Adriana Silva, Mariana Antunes, Patricia Marques, Bruno Dias, Ilka Abreu, Nazareth Rocha, Vera Capelozzi, Patricia Rocco
Journal: European Respiratory Journal (2011)

The present study investigated whether regular and moderate aerobic exercise might prevent airway remodeling in experimental chronic allergic asthma. For this purpose, 48 BALB/c mice were assigned into 2 groups: sedentary (S) and trained (Tr). Tr group ran on a motorized treadmill, at moderate intensity (8-12 m.min -1 ), 5% grade, 30 min/day, 3 times a week for 8 wks. At 8 wks, animals were further randomized into 2 subgroups to be immunized and challenged with ovalbumin (OVA) or to receive saline using the same protocol (C). Aerobic exercise continued until the end of the protocol. Echocardiographic analysis was done before, at 4 and 8 weeks of training, and after asthma induction. Twenty-four hours after the last challenge, trained, compared to sedentary mice, presented: 1) an increase in systolic output, left ventricular mass, and end-diastolic volume; 2) a reduction in airway resistance, viscoelastic pressure, static elastance, eosinophil infiltration, smooth-muscle actin expression, and collagen fiber content in airways and lung parenchyma; 3) a decrease of transforming growth factor-β levels in bronchoalveolar lavage fluid (BALF) and blood; 4) an increase in interferon-γ in BALF and blood; 5) an augment of interleukin (IL)-10 in blood but a reduction in BALF; and 6) a decrease in IL-5 and IL-13 only in BALF. In conclusion, regular and moderate aerobic exercise was effective in preventing airway and lung parenchyma remodeling in the present murine model of chronic allergic asthma, improving lung function.  Supported by: INCT-INOFAR, CNPq, PRONEX, FAPERJ, CAPES
Beyond the Guidelines in the Treatment of Peripheral T-Cell Lymphoma: New Drug Development
Authors: Andy I. Chen, Ranjana H. Advani
Journal: Journal of the National Comprehensive Cancer Network (2008)

Peripheral T-cell lymphomas (PTCLs) are a rare and diverse group of neoplasms with a poor prognosis. Management of these disorders has been largely extrapolated from the treatment of aggressive B-cell lymphomas; however, therapeutic responses to this approach are neither adequate nor durable for most patients with PTCL. Given the rarity of PTCL, much of the literature consists of studies with small sample size and anecdotal case reports. Therefore, no consensus exists on the best therapeutic strategy for either newly diagnosed or relapsed/refractory PTCL. This article reviews promising novel approaches in the treatment of PTCL and its subtypes. Investigation into the pathogenesis of PTCL has also identified new targets for treatment. These emerging therapies include new uses of existing agents and the development of novel agents specifically targeted against T-cell lymphoma. Results using antimetabolites, immunotherapies, and histone deacetylase inhibitors have been particularly encouraging. These novel therapies are being tested as single agents and in combination with conventional lymphoma regimens in the frontline and salvage settings. Because of the rarity and heterogeneity of PTCL, national and international cooperation is needed to conduct the clinical studies required for the development of more effective treatment paradigms. These efforts are ongoing and will hopefully guide new strategies to improve the historically poor outcome of PTCL.
Loop diuretic dose adjustments after a hospitalization for heart failure: insights from <scp>ASCEND‐HF</scp>
Authors: Adam D. DeVore, Vic Hasselblad, Robert J. Mentz, Christopher M. O'Connor, Paul W. Armstrong, John J. McMurray, Justin A. Ezekowitz, W.H. Wilson Tang, Randall C. Starling, Adriaan A. Voors, Robert M. Califf, Adrian F. Hernandez
Journal: European Journal of Heart Failure (2015)
Correlation between heart rate variability indexes and aerobic physiological variables in patients with COPD
Authors: Marceli Rocha Leite, Ercy Mara Cipulo Ramos, Rafaela Campos Cuissi, Carlos Augusto Kalva Filho, Fernanda Maria Machado Rodrigues, Paula Roberta da Silva Pestana, Aline Duarte Ferreira Ceccato, Luiz Carlos Soares de Carvalho, Juliana Tiyaki Ito, Juliana Nicolino, Marcelo Papoti, Luiz Carlos Marques Vanderlei, Alessandra Choqueta de Toledo, Dionei Ramos
Journal: European Respiratory Journal (2013)

Heart rate variability (HRV) has become an important clinical tool for assessing autonomic nervous system. HRV has the potential to provide additional valuable insight into physiological and pathological conditions. However, it is not known if HRV has correlation with aerobic physiological variables in patients with COPD. Therefore, this study aimed to correlate resting HRV indexes with aerobic physiological variables obtained in maximal exercise testing in patients with COPD. Thirteen patients with COPD (Age 65,6±7,4; BMI 27,5±4,4; FEV1% 50,4±15,5) performed a maximal exercise testing on a treadmill to determine maximal oxygen uptake (VO 2max ), intensity exercise corresponding to VO 2max  (IVO 2max ) and ventilatory thresholds by O 2  and CO 2  equivalents (VT1 and VT2, respectively). For HRV analysis the heart rate was measured by a heart rate monitor (Polar Electro, S810i, Finland) with the volunteers at rest and HRV indexes were analyzed using linear methods in the time (rMSSD and SDNN) and frequency (LF, HF and LF/HF ratio) domain and nonlinear methods (SD1 and SD2). Shapiro-Wilk test was used to assess the normality of the data and the correlations between HRV indexes and physiological variables were verified by Pearson or Spearman test. The level of significance was set at 5%. There were correlations between SDNN and VT2(R=0.65), rMSSD and VT1 (R=0.56), VT2 and SD1 (R=0.56), SD2 and IVO 2max  (R=0.55), SD2 and VT2 (R=0.66). We conclude that resting HRV indexes were correlated with aerobic physiological variables in patients with COPD, which suggests that this clinical tool can be used as a predictor of aerobic performance in maximal exercise testing in these patients.
Abstract 1966: Comparison of Right Ventricular Strain and Strain Rate in Patients with Arrhythmogenic Right Ventricular Cardiomyopathy, Right Ventricular Outflow Tract Tachycardia, and Matched Controls
Authors: Omid Salehian, Andrew P Klug, Jeffrey Healey, Ian G Burwash
Journal: Circulation (2007)

Background: Arrhythmogenic right ventricular cardiomyopathy (ARVC) is characterized by fibro-fatty replacement of RV myocardium leading to ventricular tachycardia and sudden death in otherwise healthy individuals. Diagnosis is challenging as there are no diagnostic tests with adequate accuracy. Current diagnosis of ARVC is made by the task force criteria. One of the main diagnostic dilemmas continues to be distinguishing ARVC from a relatively benign entity of right ventricular out flow tract tachycardia (RVOT VT). Assessment of myocardial strain and strain rate has been used to study patients with ischemic heart disease and has shown utility in identifying subtle myocardial dysfunction not detected by routine wall motion assessment. The goal of this study was to compare myocardial strain and strain rates in patients with ARVC, RVOT VT and matched controls. Methods: We prospectively enrolled 12 patients with ARVC (based on task force criteria), 10 with RVOT VT, and 22 age and gender matched controls. Echo studies (including tissue Doppler derived myocardial strain echocardiography) were performed with commercially available systems (GE, Vivid 7). Peak systolic RV myocardial strain and strain rate were measured at base, mid, and apical RV free wall and compared. Results: ARVC patients had significantly lower peak systolic RV strain compared to both RVOT VT patients and matched controls (Table ). There was also significantly lower peak systolic strain rate at the apical RV myocardium in patients with ARVC compared to both those with RVOT VT (p=0.02) and controls (p=0.01). Conclusions: Patients with ARVC have abnormally low RV systolic strain and strain rates when compared to matched controls as well as those with RVOT VT. This modality can be routinely used in assessing patients suspected of ARVC as it might assist in earlier diagnosis as well as help in distinguishing patients with ARVC from those with RVOT VT. P&lt;0.05 compared to controls, † P&lt;0.05 compared to RVOT VT group
Decrease in a quantity of the eosinophils in bioptates of the mucosa of bronchial tree of patients with bronchial asthma associated with stressful life events
Authors: Evgeny Nemerov, Valentina Boyarko, Alla Mikhailova
Journal: European Respiratory Journal (2013)

It is found in the investigations of the relation between stress and inflammation, that psycho-emotional stress strengthens a production of cytokine and inflammation mediators.  The aim: To study the special features of the cellular contents of bioptates of the mucosa of bronchi of patients with bronchial asthma (BA) associated with psychological stresses.  Twenty eight patients with BA were investigated. They were divided into 2 groups with 14 persons in each group. The first group included patients in whom the first episode of the disease were associated with stressful life events. The second group included 117 patients in whom the disease was not linked to psychological factors. The fibrobronchoscopy with taking bioptates of the mucosa of bronchial tree with following quantitative estimation of its cellular contents was inspected for all patients.  Results: Patients in the first group had significant decrease of lymphocytes than in the second one (the medians are 18.98% and 26.66%, correspondingly, p=0.03), and, especially, eosinophiles (the medians are 0.98% and 2.00%, correspondingly, p=0.007) in the own plate of the mucosa of bronchi. Ratio of other inflammation cells changes nonessentially in both groups.  Conclusion: Psycho-emotional triggers can modulate the inflammation reaction of the mucosa of bronchi of PIBA patients decreasing a participation of lymphocytes and, especially, eosinophiles in this reaction.
p300 Modulates Nuclear Morphology in Prostate Cancer
Authors: Jose D. Debes, Thomas J. Sebo, Hannelore V. Heemers, Benjamin R. Kipp, De Anna L. Haugen, Christine M. Lohse, Donald J. Tindall
Journal: Cancer Research (2005)

Alterations in nuclear structure distinguish cancer cells from noncancer cells. These nuclear alterations can be translated into quantifiable features by digital image analysis in a process known as quantitative nuclear morphometry. Recently, quantitative nuclear morphometry has been shown to predict metastasis and biochemical recurrence of prostate cancer. However, little is known about the cellular mechanisms underlying these nuclear morphometric changes. Alterations of nuclear matrix proteins are frequently involved in changes of nuclear structure. A number of co-activators interact with these nuclear structure-related proteins, suggesting that they might be involved in quantitative nuclear morphometry changes. We have shown previously that the transcriptional co-activator p300 is involved in prostate cancer progression. However, the ability of a transcriptional regulator like p300 to modulate nuclear morphology has not been described previously. In the present study, we show that p300 expression in prostate cancer biopsy tissue from 95 patients correlates with quantifiable nuclear alterations. Moreover, we show that transfection of p300 into prostate cancer cells in culture induces quantifiable nuclear alterations, such as diameter, perimeter, and absorbance among others, as assessed by digital image analysis. These alterations correlate individually with aggressive features in prostate cancer, such as expression of the proliferation marker Ki-67 and extraprostatic extension of the tumor. Finally, we found that transfection of p300 into prostate cancer cells specifically increases mRNA and protein levels of nuclear matrix peptides lamins A and C, suggesting that these proteins mediate the p300-induced effects. These findings reveal a new insight into the transcriptional and structural regulation of prostate cancer.