tbuckley/cabot-search huggingface dataset:
Revisiting Radiograph-Negative Ankle Injuries in Children
Authors: Peter J. Gill, Terry Klassen
Journal: JAMA Pediatrics (2016)

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Abstract 1248.5: Lipoprotein Changes in HIV-Infected Antiretroviral-Naïve Individuals after Starting Class-Sparing Antiretroviral Therapy: ACTG Study A5152s
Authors: James H Stein, Lauren Komarow, Bruno R Cotter, Judith S Currier, Michael P Dube, Carl J Fichtenbaum, Mariana Gerschenson, Carol K Mitchell, Robert L Murphy, Kathleen Squires, Robert A Parker, Francesca J Torriani
Journal: Circulation (2008)

Patients with human immunodeficiency virus (HIV) receiving antiretroviral therapy (ART) are at increased risk of cardiovascular disease (CVD). In HIV-infected patients on ART, abnormalities of serum lipoproteins and insulin resistance have been associated with endothelial dysfunction. However, the effects of ART on dyslipidemia and CVD risk have been difficult to study because of the complexity of ART regimens and varying metabolic effects between and within ART classes. This study evaluated the effects of three ART regimens on lipids and lipoproteins, markers of insulin and glucose metabolism, and endothelial function. This was a substudy of A5142, a prospective, multicenter study of 82 treatment-naïve HIV-infected individuals randomly assigned to receive one of 3 class-sparing HIV treatment regimens: nucleoside reverse transcriptase inhibitors (NRTIs) + the non-nucleoside reverse transcriptase inhibitor efavirenz, NRTIs + the protease inhibitor lopinavir/ritonavir (LPV/r), or NRTI-sparing regimen of efavirenz + LPV/r. Lipoprotein particle concentrations were measured by nuclear magnetic resonance spectroscopy. Endothelial function was evaluated by brachial artery flow-mediated vasodilation (FMD) at baseline and after 24 weeks. All values are medians (interquartile range). Total and small low-density lipoprotein concentrations increased by 152 (−49, +407, p&lt;0.01) and 130 (−98, +417, p&lt;0.01) nmol/L, respectively, especially in the 0.04). Very low-density lipoproteins also increased (p+0.01), with larger increases in the arms that contained LPV/r (p KW 0.022). High-density lipoproteins increased by 6.0 mcmol/L (+2.8, +10.4, p&lt;0.01), similarly in each arm. FMD increased by 1.48% (−0.20, +4.30%, p&lt;0.001) with similar changes in each arm. Changes in lipoproteins were not related to changes in markers of insulin/glucose metabolism or FMD. Effective ART is associated with increases in total and small low-density lipoproteins and very low-density lipoproteins, especially in regimens that contain LPV/r. Over 24 weeks, the vascular effects of ART-related lipid changes may be outweighed by beneficial effects on treatment of HIV infection.
Using the DOSE index to predict changes in health status and hospitalisation of COPD patients
Authors: Lisette van den Bemt, Myrte Rolink, Wouter van Dijk, Saskia van den Haak Rongen, Tjard Schermer
Journal: European Respiratory Journal (2013)

Background 

The FEV1 is associated with increased mortality and used for severity classification of COPD worldwide. A multicomponent index – like the DOSE index - has the potential to predict important future outcome in patients with COPD better than the FEV1.

Aims and objectives 

The aim of our study was to investigate if the DOSE index can predict which patients are at risk for a clinically relevant change in health status and hospitalisation (1).

Methods 

A prospective cohort study was done with data from primary care and secondary care. The DOSE score (dyspnea score (D), level of airflow obstruction (O), current smoking status (S) and exacerbations (E)) was determined at baseline and the 2-year change in Clinical COPD Questionnaire (CCQ)-score was calculated as well as COPD hospitalisation risk in the second year of follow-up. Linear regression analysis was performed for the effect of a high DOSE score (i.e. ≥4) on change in CCQ score. Chi-square was used to test difference in hospitalisation risk based on this DOSE cut-off point.

Results 

The study population consisted of 209 patients (112 patients from primary care). Overall a high DOSE score was a significant predictor for a change in CCQ score after 2 years (0.41, 95%CI; 0.13, 0.70), in particular in primary care patients. Significant more patients were hospitalised with a DOSE-score ≥4. (28.0%) compared to a lower DOSE score (2.7%; p<0.01).

Conclusions 

A DOSE score ≥4 has the ability to identify COPD patients with a greater risk on future worsening in health status and hospitalisation risk.

1) Rolink M. et al. Using the DOSE index to predict changes in health status of COPD patients. Primary Care Respiratory Journal (In press).
Detection of New Cross-Reacting Carcinoembryonic Antigen(s) on Cultured Tumor Cells by Mixed Hemadsorption Assay2
Authors: P. B. Dent, S. Carrel, J.-P. Mach
Journal: JNCI Journal of the National Cancer Institute (1980)

Antisera highly specific for carcinoembryonic antigen (CEA) from New Zealand White rabbits and a goat reacted strongly in antibody binding tests with cultured tumor cell lines, irrespective of the ability of the cell lines to produce CEA. The most reactive were colon carcinoma and melanoma cell lines, the former known to produce CEA and the latter not associated with CEA production. The reactivity was not diminished by absorption with perchloric acid extracts of normal lung or spleen, whereas absoprtion with purified CEA preparations abolished the reactivity. Quantitative absorption studies indicated that reactivity against CEA-producing cell lines could be totally removed by absorption with other CEA-producing lines but not with melanoma cell lines. Reactivity against melanoma cell lines could be completely removed by colon carcinoma cells as well as by melanoma cells. Antisera raised against purified CEA, after absorption with extracts of normal lung, still contained two populations of antibodies, one that binds a newly described antigen cross-reacting with CEA which is present on melanoma cells.
Systematic Mapping Of Drug and Pathway Sensitivity In Chronic Lymphocytic Leukemia Identifies Synthetic Lethal Interactions Of Mutant p53
Authors: Leopold Sellner, Oles Malgorzata, Mikolaj Slabicki, Carolin Blume, Hüllein Jennifer, Tatjana Stolz, Martin Sill, Sascha Dietrich, Olaf Merkel, Anna Jauch, Manfred Hensel, Davide Rossi, Zirlik Katja, Martina Seiffert, Anthony D. Ho, von Kalle Christof, Hanno Glimm, Wolfgang Huber, Thorsten Zenz
Journal: Blood (2013)
Abstract 14149: Mitochondrial Targeted DNA Repair Enzyme, Endonuclease III (ENDO III), Attenuates Myocardial Ischemia/Reperfusion Injury
Authors: Hiroyuki Otsuka, Shashi Bhushan, Adrienne L King, David Polhemus, Glenn L Wilson, David J Lefer
Journal: Circulation (2013)

Background: Previous studies have demonstrated that oxidative stress, mitochondrial dysfunction, and mitochondrial DNA (mtDNA) abnormalities contribute to cell death. Mitochondrial targeted DNA repair enzymes play a pivotal role in repairing oxidative damage to mtDNA. We hypothesized that mtDNA damage during myocardial ischemia/reperfusion (MI/R) injury could be attenuated by enhancing mtDNA repair via mitochondrial targeted DNA repair with the Endo III repair enzyme. Methods: Male C57/BL6J (10-12 weeks) were subjected to 45 min. of MI and 24 hr. of R in vivo. Endo III (4 mg/kg) or vehicle (VEH) was administered 5 min. before R. Serum troponin-I was measured and infarct size per area-at-risk (INF/AAR) was evaluated at 24 hr. R. Two-dimensional echocardiography was performed at baseline, 1, 2, and 4 weeks post MI to assess left ventricular (LV) dimensions and ejection fraction (EF%). Results: Endo III reduced INF/AAR by 50% (p < 0.01 vs. VEH) and significantly reduced troponin-I levels (p < 0.01 vs. VEH). ...
Physical performance tests predict injury in National Collegiate Athletic Association athletes: a three-season prospective cohort study
Authors: Eric J Hegedus, Suzanne McDonough, Chris Bleakley, G David Baxter, J Tyler DePew, Ian Bradbury, Chad Cook
Journal: British Journal of Sports Medicine (2016)

The ability to predict injury is difficult. Prior injury is the only risk factor that has been reported consistently in multiple research studies. Convenient and easy to perform, physical performance tests (PPTs) have great allure as prognostic factors.11 PPTs were issued to 359 participants over the course of three seasons of National Collegiate Athletic Association Division I athletic competition. Injuries were monitored and reported in a centralised university tracking system. Exploratory factor analysis was performed in order to group the PPTs into constructs. The relationship between injury and these PPT-based constructs and other known predictors of injury was explored using univariate and multivariate regression.PPTs clustered into five constructs: (1) active motion, (2) power, (3) hip stability, (4) flexibility and (5) motor control. When these five were placed into a multiple regression equation along with known risk factors (age, body mass index (BMI), gender, excessive flexibility and past injury), hip stability and active motion were predicted injury. In addition, motor control predicted non-traumatic injury. Past injury did not predict injury in the multivariate model.In college athletes, hip stability, active motion and motor control as assessed through PPTs can be useful as part of preseason screening. These PPT-related constructs seem to have a mediating effect on the relationship between past injury and future injury. This study provides the rationale to test targeted interventions to address these limitations.NCT01804894.
Colorectal cancer patient follow-up after surgery with curative intent
Authors: F. E. Johnson, G. Rosati, G. Ambrosini, M. Mandala, N. Pinna, B. Daniele, G. Pavia, K. S. Virgo, W. E. Longo, E. M. Grossmann, R. Fossati
Journal: Journal of Clinical Oncology (2005)

3695 Background: In wealthy societies, most patients with colorectal cancer are treated with curative intent and enter some type of follow-up regimen but the optimum surveillance strategy has not been defined. There are no active adequately-powered trials dealing with this topic originating in North America, as far as we are aware, but one is open in Europe (Gruppo Italiano di Lavoro per la Diagnosi Anticipata - GILDA). Methods: After primary curative-intent treatment, stratification, and randomization at GILDA headquarters, colon cancer patients are followed according to a more intensive or less intensive surveillance regimen. Rectal cancer patients are also followed according to a more intensive or less intensive regimen; these arms are similar to the arms for colon cancer patients but focus more on local-regional recurrence. To ensure adequate statistical power, the target number of patients is 1,500. Health-related quality of life and cost-effectiveness measures are incorporated in the trial. Results: The trial opened in 1998; 1,089 patients from 42 centers had been enrolled as of October, 2004. There were 537 and 552 patients in the more and less intensive trial arms, respectively. The trial opened to North American centers in 2002. The mean duration of follow-up was 21 months as of October, 2004. Seventy-nine relapses, 37 deaths, and 9 second primary cancers had been documented in the two more intensive follow-up arms; 72 relapses, 27 deaths, and 11 second primary cancers had been observed in the two less intensive arms as of October, 2004. Conclusions: This trial should provide the first evidence based on an adequately powered randomized trial to determine the optimal follow-up strategy for colorectal cancer patients. The authors will provide information packets at the meeting for individuals and institutions interested in participating in this trial. No significant financial relationships to disclose.
Clinical outcomes of breast cancer patients with hepatitis C: A case series
Authors: P. K. H. Morrow, R. L. Theriault, G. N. Hortobagyi, K. H. Rolston, J. J. Tarrand, S. H. Taylor, E. S. Thomas, K. M. Gwyn
Journal: Journal of Clinical Oncology (2005)

747 Background An estimated 3.8 million Americans have been infected with hepatitis C virus (HCV). Despite the increasing incidence of this disease, little is known about the effects of chemotherapy in HCV patients with breast cancer. Methods HCV data from the Department of Laboratory Medicine was cross-referenced with the M.D. Anderson Cancer Center tumor registry and evaluated using computerized records. Results Twenty HCV patients with invasive breast cancer (median age, 49 years) were treated at MDACC between 2000 and 2004. Patients’ staging at initial diagnosis were as follows: stage I (3/20), stage II (7/20), stage III (7/20), and undocumented stage (3/20). Of the 5 patients who received neoadjuvant chemotherapy, 3 patients demonstrated a 50–70% clinical response, and 2 patients had undocumented responses. Overall, of the 6 patients who received anthracyclines (but no taxanes) in the adjuvant or neoadjuvant setting, only 2 complications (line infection and mucositis) were noted. Of the 9 patients who received both taxanes and anthracyclines, complications included neutropenic fever (3/9) and neuropathy (4/9). One patient received taxane therapy alone (complicated by neuropathy and hives). Four patients took hormonal therapy alone, with no complications. Altogether, 14 patients currently have no evidence of disease, 2 patients have stable metastatic disease, 1 patient died from progression of disease, 1 patient died after a car accident, 1 patient died after stem cell transplant, and 1 patient’s status is unknown. Three patients received pegylated interferon and ribavirin therapy for hepatitis C following primary breast cancer therapy; these patients required growth factors during hepatitis therapy, and 2 patients terminated treatment due to myelosuppression resistant to growth factor support. Conclusions Although complications such as febrile neutropenia and peripheral neuropathy are more common in HCV patients who receive anthracycline and taxane-based regimens for invasive breast cancer, these regimens have shown efficacy in this patient population. Our data suggests that patients with HCV and invasive breast cancer may be treated with chemotherapy, when treatment is coordinated with hepatologic management. No significant financial relationships to disclose.
Abstract 15023: Surgical Versus Transcatheter Closure for Post-Infarctus Ventricular Septal Defect
Authors: Philippe Aldebert, Alberto Riberi, Olivier Brissy, Gilles Levy, Jean Christophe Macia, Alain Fraisse
Journal: Circulation (2012)

INTRODUCTION: Post infarction ventricular septal defect (PIVSD) is a difficult to treat condition. Surgical closure is the first intention therapy but mortality rates remain high at 20-87% in curre...
Down Regulation of TOPK, PBX3, SRPK, DDX21 and CLC Genes in Newly Diagnosed, Early-Chronic Phase Chronic Myeloid Leukemia Patients Treated with Imatinib Mesylate.
Authors: Angela Poerio, Marilina Amabile, Simona Soverini, Matteo Renzulli, Gianantonio Rosti, Simona Bassi, Emanuela Ottaviani, Tiziana Grafone, Carolina Terragna, Cristian Taccioli, Michela Rondoni, Costanza Bosi, Nicoletta Testoni, Simona Luatti, Fausto Castagnetti, Michele Malagola, Fabrizio Pane, Giuseppe Saglio, Michele Baccarani, Giovanni Martinelli
Journal: Blood (2004)
Molecular prognostic and predictive markers in gynecologic cancers: The translational 1 (T-1) study of the Multicentre Italian Trials in Ovarian Cancer and Gynecologic Malignancies (MITO) group.
Authors: A. Mosconi, L. Crino, V. Ludovini, G. Scambia, G. Ferrandina, E. Breda, R. Sabbatini, C. Caserta, V. De Angelis, S. Pignata
Journal: Journal of Clinical Oncology (2010)

TPS340 Background: Platinum-based chemotherapy (CT) remains the cornerstone for treatment of many gynecologic tumors including ovarian, cervical, and endometrial cancer. Although response rates to platinum-based regimens are greater than 70%, a relevant clinical problem is the development of resistance. The nucleotide excision repair (NER), which removes cisplatin-induced DNA adducts, appears to be the principal pathway involved with platinum resistance. Single nucleotide polymorphisms (SNPs) of the genes involved in the NER may modulate repair capacity and contribute to individual variations in platinum response. The metabolic inactivation of gemcitabine is catalyzed by cytidine deaminase (CDA) but few studies have evaluated the pharmacogenetics of this enzyme with controversial results. For the objectives of this study, we selected SNPs of key genes (ERCC1, XPA, XPD, XPG, RRM1, CDA, and p53) involved in the mechanism of action or metabolism of platinum and gemcitabine 1) to evaluate the prognostic role of each SNP and 2) its possible predictive value in patients (pts) with ovarian, cervical or endometrial cancer, treated with platinum and/or gemcitabine-based CT. Methods: Eligibility criteria includehistologically proven primary gynaecologic malignancy of the ovary, cervix, and uterine corpus, including all stages, grades, and common epithelial cell types. Pts treated with CT need to receive platinum and/or gemcitabine-based CT. The protocol was approved by the local Institutional Ethical Committee. After signed informed consent, peripheral blood samples are obtained from all pts. Genomic DNA is extracted from whole blood samples (5 ml) using the QIAamp DNA estraction kit on Biorobot EZ1 (Qiagen). 8 SNPs of 7 genes (ERCC1 C118T, ERCC1 C8092A, XPA C114T, XPG Asp1104His, XPD Lys751Gln, CDA Lys27Gln, RRM1 C524T, and P53 Arg72Pro) are detected with TaqMan-probe based assays using the 7300 Real-Time PCR System (Applied Biosystems, Foster City, CA). Approximately 400 pts are expected to be enrolled in about 5 years. From March to December 2009, 92 pts (65 ovary, 20 uterine corpus, 7 cervix) were included in the study. Author Disclosure Employment or Leadership Position Consultant or Advisory Role Stock Ownership Honoraria Research Funding Expert Testimony Other Remuneration Lilly, Schering-Plough Schering-Plough
Pharmacology of hallucinations induced by long-term drug therapy
Authors: C G Goetz, C M Tanner, H L Klawans
Journal: American Journal of Psychiatry (1982)

The authors studied 20 patients with Parkinson's disease and prominent hallucinations related to dopaminergic or anticholinergic therapy. The character of the hallucinations appeared distinct from the classic description of either acute anticholinergic or acute aminergic hallucinatory states. Manipulation of either kind of drug could precipitate or relieve hallucinations in a given patient, which suggests that the dopaminergic/cholinergic systems are reciprocally active in the pathophysiology of long-term drug-induced hallucinatory states in this population.
Coadministration of Trametinib and Palbociclib Radiosensitizes KRAS-Mutant Non–Small Cell Lung Cancers <i>In Vitro</i> and <i>In Vivo</i>
Authors: Zhen Tao, Justin M. Le Blanc, Chenguang Wang, Tingting Zhan, Hongqing Zhuang, Ping Wang, Zhiyong Yuan, Bo Lu
Journal: Clinical Cancer Research (2016)

To investigate the potential roles that p16 (CDKN2A) and RB activation have in sensitization to MEK inhibitor in resistant KRAS-mutant non-small cell lung cancer cells (NSCLC) in vitro and in vivo.Cell viability was measured with MTS assays. Effects of administration of radiation and combination drug treatments were evaluated by clonogenic assay, flow cytometry, and Western blots. DNA repair was assessed using immunofluorescent analysis. Finally, lung cancer xenografts were used to examine in vivo effects of drug treatment and radiation therapy.In this study, we showed that sensitivity to MEK inhibitor correlated to the RB/p16/CDK4 pathway and knockdown of RB induced resistance in cell lines sensitive to MEK inhibitor. Also, overexpression of p16 and inhibition of CDK4 had the ability to sensitize normally resistant cell lines. Our data indicated that the MEK inhibitor (trametinib, GSK112012) cooperated with the CDK4/6 inhibitor (palbociclib, PD0332991) to strongly reduce cell viability of KRAS-mutant NSCLCs that were resistant to the MEK inhibitor in vitro and in vivo. In addition, we report for the first time that resistance of KRAS-mutant NSCLCs to MEK inhibitor is, at least partly, due to p16 mutation status, and we described a drug combination that efficiently reactivates the RB tumor suppressor pathway to trigger radiosensitizing effects, apoptosis, and cell-cycle arrest.Our findings suggest that MEK inhibitor in combination with CDK4/6 inhibitor has significant anti-KRAS-mutant NSCLC activity and radiosensitizing effect in preclinical models, potentially providing a novel therapeutic strategy for patients with advanced KRAS-mutant NSCLCs.
Adjuvant systemic therapy in elderly patients with breast cancer: A Brazilian single center experience
Authors: G. Ismael, A. L. Coradazzi, C. A. Beato, P. Milhomem, J. Oliveira, C. Manzoni, G. Segalla
Journal: Journal of Clinical Oncology (2009)

e20711 Background: Breast cancer is the leading cause of cancer in women in Brazil and in the western world. Despite the high incidence of breast cancer in elderly women, there is no solid information regarding the real impact of the adjuvant systemic therapy in this population, considering the underrepresentation of patients with 65 years of age or older in cancer-treatment trials. Moreover, elderly patients may face some difficulties to receive adequate adjuvant systemic treatment in the routine clinical practice. Methods: Two hundred fifty eight patients with 65 years of age or older at the time of diagnosis of operable breast cancer and treated in our Institution from February 2000 to December 2005 were retrospectively studied. Clinical and pathological data were recorded as well as the type of adjuvant systemic therapy: hormonal therapy (HT), chemotherapy (CT) or both. We evaluated the disease free survival and overall survival and compared the results between the group of patients treated with HT only and the group of patients treated with both HT and CT. Results: Ninety five (37.5%) patients were stage I, 150 (58.1%) were stage II and 6 (2.3%) were stage III, while 5 (1.9%) patients were diagnosed with DCIS. Ductal carcinoma was the most frequent histological type (81%) and grade II were reported in the majority of patients (47.3%). Mostly of patients were hormonal sensible (74.4% were ER+ and 64% were PR+) and HER 2 negative (81.8%). One hundred seventy eight (69%) patients received any kind of adjuvant HT while 91 (35.3%) received any kind of adjuvant CT. There was no statistical difference between patients treated with HT when compared with the group of patients treat with HT and CT, regarding disease free survival and overall survival. However, a higher rate of high risk patients were observed in the group treated with both HT and CT. Conclusions: Despite the age, a considerable part of this elderly breast cancer patient's population has received adjuvant systemic treatment. Benefits from HT and/or CT may be considered in this group of patients. No significant financial relationships to disclose.