tbuckley/cabot-search huggingface dataset:
Alfapump® system vs. large volume paracentesis for refractory ascites: A multicenter randomized controlled study
Authors: Christophe Bureau, Danielle Adebayo, Mael Chalret de Rieu, Laure Elkrief, Dominique Valla, Markus Peck-Radosavljevic, Anne McCune, Victor Vargas, Macarena Simon-Talero, Juan Cordoba, Paolo Angeli, Silvia Rosi, Stewart MacDonald, Massimo Malago, Maria Stepanova, Zobair M. Younossi, Claudia Trepte, Randall Watson, Oleg Borisenko, Sun Sun, Neil Inhaber, Rajiv Jalan
Journal: Journal of Hepatology (2017)
IS total body irradiation (tbi) a necessary component of preparative therapy for autologous transplantation in non-hodgkin's lymphoma (NHL)?
Authors: Richard S. Stein, John P. Greer, Stacey A. Goodman, Stephen J. Brandt, David S. Morgan, William R. Macon, Thomas L. McCurley, Steven N. Wolff
Journal: Blood (2000)
Common Molecular Subtypes Among Asian Hepatocellular Carcinoma and Cholangiocarcinoma
Authors: Jittiporn Chaisaingmongkol, Anuradha Budhu, Hien Dang, Siritida Rabibhadana, Benjarath Pupacdi, So Mee Kwon, Marshonna Forgues, Yotsawat Pomyen, Vajarabhongsa Bhudhisawasdi, Nirush Lertprasertsuke, Anon Chotirosniramit, Chawalit Pairojkul, Chirayu U. Auewarakul, Thaniya Sricharunrat, Kannika Phornphutkul, Suleeporn Sangrajrang, Maggie Cam, Ping He, Stephen M. Hewitt, Kris Ylaya, Xiaolin Wu, Jesper B. Andersen, Snorri S. Thorgeirsson, Joshua J. Waterfall, Yuelin J. Zhu, Jennifer Walling, Holly S. Stevenson, Daniel Edelman, Paul S. Meltzer, Christopher A. Loffredo, Natsuko Hama, Tatsuhiro Shibata, Robert H. Wiltrout, Curtis C. Harris, Chulabhorn Mahidol, Mathuros Ruchirawat, Xin W. Wang
Journal: Cancer Cell (2017)
Linked read sequencing resolves complex genomic rearrangements in gastric cancer metastases
Authors: Stephanie U. Greer, Lincoln D. Nadauld, Billy T. Lau, Jiamin Chen, Christina Wood-Bouwens, James M. Ford, Calvin J. Kuo, Hanlee P. Ji
Journal: Genome Medicine (2017)

Genome rearrangements are critical oncogenic driver events in many malignancies. However, the identification and resolution of the structure of cancer genomic rearrangements remain challenging even with whole genome sequencing. To identify oncogenic genomic rearrangements and resolve their structure, we analyzed linked read sequencing. This approach relies on a microfluidic droplet technology to produce libraries derived from single, high molecular weight DNA molecules, 50 kb in size or greater. After sequencing, the barcoded sequence reads provide long range genomic information, identify individual high molecular weight DNA molecules, determine the haplotype context of genetic variants that occur across contiguous megabase-length segments of the genome and delineate the structure of complex rearrangements. We applied linked read sequencing of whole genomes to the analysis of a set of synchronous metastatic diffuse gastric cancers that occurred in the same individual. When comparing metastatic sites, our analysis implicated a complex somatic rearrangement that was present in the metastatic tumor. The oncogenic event associated with the identified complex rearrangement resulted in an amplification of the known cancer driver gene FGFR2. With further investigation using these linked read data, the FGFR2 copy number alteration was determined to be a deletion-inversion motif that underwent tandem duplication, with unique breakpoints in each metastasis. Using a three-dimensional organoid tissue model, we functionally validated the metastatic potential of an FGFR2 amplification in gastric cancer. Our study demonstrates that linked read sequencing is useful in characterizing oncogenic rearrangements in cancer metastasis.
DGGE analysis of mitochondrial tRNA gene and p53 gene mutations in newborns receiving prepartum AZT-based HIV-1 prophylaxis
Authors: Salina Torres, Dennis Cook, Consuelo McCash, Dale Walker, Vernon Walker
Journal: Cancer Research (2007)

AACR Annual Meeting-- Apr 14-18, 2007; Los Angeles, CA

4265 

Highly active antiretroviral therapy (HAART), typically containing two nucleoside analogs including zidovudine (AZT), is highly effective in inhibiting viral replication in HIV-infected patients and reducing perinatal transmission of the virus from mother to child; however, emerging evidence suggests that AZT-based HAART increases risk for mitochondrial disease and cancer in treated patients and children through induction of persistent DNA damage. Denaturing gradient gel electrophoresis (DGGE) methods were developed for detecting sequence variants in the 22 mitochondrial tRNA genes and exons 5-8 of the p53 tumor suppressor gene, and a pilot study was conducted to determine if mitochondrial DNA (mtDNA) and/or p53 gene mutations can be detected in accessible tissue/cells from HIV-uninfected newborns receiving prepartum AZT-based prophylaxis versus healthy unexposed control infants. DGGE analysis of umbilical cord tissue identified two previously reported normal variants/polymorphisms in all children (n=9 controls and 8 exposed), plus eight additional sets of distinct variants not found in controls representing ‘hotspots’ for AZT-induced mtDNA mutations ( P <0.001); these included 2 transitions, 5 transversions, and a single-base insertion distinct from previously reported spontaneous mutations or those associated with inherited mitochondrial disease. Similar mutant/wild-type heteroduplex migration patterns were found in cord blood lymphocytes, indicating the occurrence of the same mutations in AZT-exposed infants. Using suggested criteria [Trends in Genetics 20:591-596, 2004], 3 of 4 mutated tRNAs had some pathogenic characteristics. Induction of tRNA gene mutations may lead to altered mitochondrial function, production of reactive oxygen species, and resistance to apoptosis, all which may contribute to carcinogenesis. DGGE analysis of the p53 gene in cord blood lymphocytes demonstrated a total of 42 mutations in 10 AZT-exposed newborns, representing six mutational ‘hotspots’ in exons 5, 6, or 8. No p53 gene mutations were detected in control infant lymphocytes (n=24). These preliminary results correlate with the recent findings of a high degree of multiplicity for p53 gene mutations, including three ‘hotspots’, in individual lung neoplasms from mice exposed in utero to AZT (H-H Hong et al, Environ Mol Mutagen, PMID:16395694). The fact that both p53 and tRNA gene mutations were found in the same 'normal' cell type suggests that these mutations were early events induced during fetal development, predisposing AZT-exposed infants to the development of cancer later in life. The findings of both p53 and tRNA gene mutations in the same type of cells raises the question of whether the mtDNA mutations preceded and predisposed to alterations in p53 and other nuclear genes, and indicate the need for long-term surveillance of children receiving perinatal AZT.
Comparing the Effects of Mindfulness-Based Cognitive Therapy and Sleep Psycho-Education with Exercise on Chronic Insomnia: A Randomised Controlled Trial
Authors: Samuel Yeung-shan Wong, De-xing Zhang, Carole Chi-kwan Li, Benjamin Hon-kei Yip, Dicken Cheong-chun Chan, Yuet-man Ling, Cola Siu-lin Lo, Doris Mei-sum Woo, Yu-ying Sun, Helen Ma, Winnie Wing-sze Mak, Ting Gao, Tatia Mei-chun Lee, Yun-kwok Wing
Journal: Psychotherapy and Psychosomatics (2017)

&lt;b&gt;&lt;i&gt;Background:&lt;/i&gt;&lt;/b&gt; Mindfulness-based cognitive therapy (MBCT) is a potential treatment for chronic insomnia. We evaluated the efficacy of MBCT for insomnia (MBCT-I) by comparing it with a sleep psycho-education with exercise control (PEEC) group. &lt;b&gt;&lt;i&gt;Methods:&lt;/i&gt;&lt;/b&gt; Adults with chronic primary insomnia (&lt;i&gt;n&lt;/i&gt; = 216) were randomly allocated to the MBCT-I or PEEC group. The MBCT-I included mindfulness and psycho-education with cognitive and behavioural components under cognitive behavioural therapy for insomnia. PEEC included psycho-education of sleep hygiene and stimulus control, and exercises. Any change in insomnia severity was measured by the Insomnia Severity Index (ISI). Secondary outcomes included sleep parameters measured by a sleep diary, health service utilisation, absence from work and mindfulness measured by the Five Facet Mindfulness Questionnaire. &lt;b&gt;&lt;i&gt;Results:&lt;/i&gt;&lt;/b&gt; The ISI score significantly decreased in the MBCT-I group compared with the PEEC group at 2 months (i.e., post-intervention) (&lt;i&gt;p&lt;/i&gt; = 0.023, effect size [95% CI] -0.360 [-0.675, -0.046]) but not at 5 or 8 months. Treatment response rates and remission rates based on the ISI cut-off scores were not significantly different between groups. Wake time after sleep onset (WASO) was less in the MBCT-I group at 2 and 5 months. At 8 months, both groups showed a reduced ISI score, sleep onset latency and WASO, and increased sleep efficiency and total sleep time; however, no group differences were seen. Other outcome measures did not significantly improve in either group. &lt;b&gt;&lt;i&gt;Conclusions:&lt;/i&gt;&lt;/b&gt; Long-term benefits were not seen in MBCT-I when compared with PEEC, although short-term benefits were seen.
Etude prospective des lésions détectées par entéroscopie capsulaire 6 mois après résection iléocaecale dans la maladie de Crohn
Authors: A Bourreille, M Jarry, PN d'halluin, V Maunoury, P Bulois, S Sacher-Huvelin, D Heresbach, JF Bretagne, JF Colombel, JP Galmiche
Journal: Endoscopy (2005)

Après iléo-colectomie pour maladie de Crohn (MC), une récidive endoscopique survient sur l'iléon pré-anastomotique dans 60% des cas à un an. Sa gravité est corrélée au risque de récidive clinique. L'examen de l'intestin grêle par entéroscopie capsulaire (EC) permet de mettre en évidence des lésions méconnues par les examens habituels. Les buts de cette étude étaient 1) de comparer les performances de l'iléocoloscopie et de l'EC dans la détection d'une récidive après chirurgie pour MC; 2) de mesurer la concordance interobservateurs pour la classification des lésions de l'intestin grêle par EC.
Regadenoson Induces Comparable Left Ventricular Perfusion Defects as Adenosine
Authors: John J. Mahmarian, Manuel D. Cerqueira, Ami E. Iskandrian, Timothy M. Bateman, Gregory S. Thomas, Robert C. Hendel, Lemuel A. Moye, Ann W. Olmsted
Journal: JACC. Cardiovascular imaging (2009)
Oral ofloxacin and clindamycin as an alternative to the classic rifampicin–clindamycin in hidradenitis suppurativa: retrospective analysis of 65 patients
Authors: J. Delaunay, A.P. Villani, P. Guillem, A. Tristan, A. Boibieux, D. Jullien
Journal: British Journal of Dermatology (2017)

Rifampicin/Clindamycin (RC) combination is recommended as first line therapy in moderate to severe Hidradenitis Suppurativa (HS) by European S1 guidelines (1–3), notably because a large variety of microorganisms have been isolated from HS lesions: most represented bacteria appear to be Staphylococcus aureus, Coagulase negative staphylococci (CoNS) and anaerobic bacteria from normal skin flora. It has been hypothesized that these bacteria could play a central role in the initiation and maybe in the maintenance of HS lesions, possibly by being a source of antigens in a dysregulated immune response.

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Early Myocardial Strain Changes During Potentially Cardiotoxic Chemotherapy May Occur as a Result of Reductions in Left Ventricular End-Diastolic Volume
Authors: Jennifer H. Jordan, Bunyapon Sukpraphrute, Giselle C. Meléndez, Marie-Pierre Jolly, Ralph B. D’Agostino, W. Gregory Hundley
Journal: Circulation (2017)
Randomized, Noncomparative, Phase II Trial of Early Switch From Docetaxel to Cabazitaxel or Vice Versa, With Integrated Biomarker Analysis, in Men With Chemotherapy-Naïve, Metastatic, Castration-Resistant Prostate Cancer
Authors: Emmanuel S. Antonarakis, Scott T. Tagawa, Giuseppe Galletti, Daniel Worroll, Karla Ballman, Marie Vanhuyse, Guru Sonpavde, Scott North, Costantine Albany, Che-Kai Tsao, John Stewart, Atef Zaher, Ted Szatrowski, Wei Zhou, Ada Gjyrezi, Shinsuke Tasaki, Luigi Portella, Yang Bai, Timothy B. Lannin, Shalu Suri, Conor N. Gruber, Erica D. Pratt, Brian J. Kirby, Mario A. Eisenberger, David M. Nanus, Fred Saad, Paraskevi Giannakakou
Journal: Journal of Clinical Oncology (2017)

Purpose The TAXYNERGY trial ( ClinicalTrials.gov identifier: NCT01718353) evaluated clinical benefit from early taxane switch and circulating tumor cell (CTC) biomarkers to interrogate mechanisms of sensitivity or resistance to taxanes in men with chemotherapy-naïve, metastatic, castration-resistant prostate cancer. Patients and Methods Patients were randomly assigned 2:1 to docetaxel or cabazitaxel. Men who did not achieve ≥ 30% prostate-specific antigen (PSA) decline by cycle 4 (C4) switched taxane. The primary clinical endpoint was confirmed ≥ 50% PSA decline versus historical control (TAX327). The primary biomarker endpoint was analysis of post-treatment CTCs to confirm the hypothesis that clinical response was associated with taxane drug-target engagement, evidenced by decreased percent androgen receptor nuclear localization (%ARNL) and increased microtubule bundling. Results Sixty-three patients were randomly assigned to docetaxel (n = 41) or cabazitaxel (n = 22); 44.4% received prior potent androgen receptor–targeted therapy. Overall, 35 patients (55.6%) had confirmed ≥ 50% PSA responses, exceeding the historical control rate of 45.4% (TAX327). Of 61 treated patients, 33 (54.1%) had ≥ 30% PSA declines by C4 and did not switch taxane, 15 patients (24.6%) who did not achieve ≥ 30% PSA declines by C4 switched taxane, and 13 patients (21.3%) discontinued therapy before or at C4. Of patients switching taxane, 46.7% subsequently achieved ≥ 50% PSA decrease. In 26 CTC-evaluable patients, taxane-induced decrease in %ARNL (cycle 1 day 1 v cycle 1 day 8) was associated with a higher rate of ≥ 50% PSA decrease at C4 ( P = .009). Median composite progression-free survival was 9.1 months (95% CI, 4.9 to 11.7 months); median overall survival was not reached at 14 months. Common grade 3 or 4 adverse events included fatigue (13.1%) and febrile neutropenia (11.5%). Conclusion The early taxane switch strategy was associated with improved PSA response rates versus TAX327. Taxane-induced shifts in %ARNL may serve as an early biomarker of clinical benefit in patients treated with taxanes.
Cost-effectiveness analysis of bendamustine plus rituximab versus CHOP-R in treatment-naive patients with mantle cell (MCL) and indolent lymphomas (IL).
Authors: Wayne Su, Peter Quon, John Whalen, Gayatri Ranganathan, Samantha Wronski, Mkaya Mwamburi, Kevin B. Knopf, James A. Sterchele, Christopher G. Salvador, Ipek Ozer Stillman, Ananth Kadambi
Journal: Journal of Clinical Oncology (2012)

6553 Background: To assess the cost-effectiveness of bendamustine plus rituximab (B-R) vs cyclophosphamide, doxorubicin, vincristine, prednisone, and rituximab (CHOP‑R) for treatment-naive patients with MCL or IL from a US healthcare payer perspective. Methods: A discrete event simulation was developed for a mixed population of patients with MCL or IL. Two arms were simulated, each containing 1000 identical MCL or IL patients treated with B-R or CHOP-R. Input data for baseline characteristics, overall response, and risks for treatment-related adverse events (AEs) and infections were obtained from the NHL 1-2003 trial (n=549, primarily stage IV MCL and IL); gaps were filled by consultation with experts. Direct medical costs and utilities were estimated based on US databases and published literature. Costs and benefits were discounted at 3% per annum. Base case model predictions were performed by selecting regression models that had a best fit to progression free survival (PFS). Robustness of these models was evaluated by testing other models with reasonably good fit. Results: In the base case, model predicts longer PFS for B-R than for CHOP-R in MCL (average of 49.8 vs 28.6 months) and IL (67.9 vs 51.0). Quality-adjusted life-years (QALYs) per patient were higher for B-R than CHOP-R for MCL (3.51 vs 2.68) and IL (4.42 vs 3.58). For MCL, total per-patient costs were $115,191 for B-R and $100,261 for CHOP-R; for IL, respective costs were $134,814 and $110,065, resulting in incremental cost-effectiveness ratios (ICERs) for B-R vs CHOP-R of $18,161 per QALY for MCL and $29,549 for IL (ICER&lt;$50,000 to be cost-effective). Higher complete and partial response rates for B-R than for CHOP-R impacted subsequent treatment costs, which were lower for B-R by $21,632 for MCL and $24,961 for IL, as well as AE costs, lower by $10,113 and $10,570, respectively. The model results were robust with respect to the use of alternative regression models for PFS estimation. Conclusions: In patients with MCL or IL, the model demonstrates that B-R is a cost-effective alternative to CHOP-R. Alternative regression models confirmed robustness of results. Support: Teva Pharmaceutical Industries Ltd.
Expanded yield of multiplex panel testing in fully accrued prospective trial.
Authors: Gregory Idos, Allison W. Kurian, Charite Nicolette Ricker, Duveen Sturgeon, Julie Culver, Kerry Kingham, Rachel Koff, Nicolette M. Chun, Courtney Rowe-Teeter, Katrina Lowstuter, Anne-Renee Hartman, Brian Allen, John Kidd, Meredith Mills, Cindy Ma, Christine Hong, Kevin McDonnell, Uri Ladabaum, James M. Ford, Stephen B. Gruber
Journal: Journal of Clinical Oncology (2017)

1525 Background: Genetic testing is a powerful tool for stratifying cancer risk. Multiplex gene panel (MGP) testing allows simultaneous analysis of multiple high- and moderate- penetrance genes. However, the diagnostic yield and clinical utility of panels remain to be further delineated. Methods: A report of a fully accrued trial (N = 2000) of patients undergoing cancer-risk assessment. Patients were enrolled in a multicenter prospective cohort study where diagnostic yield and off-target mutation detection was evaluated of a 25 gene MGP comprised of APC, ATM, BARD1, BMPR1A, BRCA1, BRCA2, BRIP1, CDH1, CDK4, CDKN2A, CHEK2, EPCAM, MLH1, MSH2, MSH6, MUTYH, NBN, PALB2, PMS2, PTEN, RAD51C, RAD51D, SMAD4, STK11, TP53. Patients were enrolled if they met standard testing guidelines or were predicted to have a ≥2.5% mutation probability by validated models. Differential diagnoses (DDx) were generated after expert clinical genetics assessment, formulating up to 8 inherited cancer syndromes ranked by estimated likelihood. Results: 1998/2000 patients had reported MGP test results. Women constituted 81% of the sample, and 40% were Hispanic; 241 tested positive for at least 1 pathogenic mutation (12.1%) and 689 (34.5%) patients carried at least 1 variant of uncertain significance. The most frequently identified mutations were in BRCA1 (17%, n = 41), BRCA2 (15%, n = 36), APC (8%, n = 19), CHEK2 (7%, n = 17), ATM (7%, n = 16). 39 patients (16%) had at least 1 pathogenic mutation in a mismatch repair (MMR) gene ( MLH1, n = 10; MSH2, n = 10; MSH6, n = 8; PMS2, n = 11). 43 individuals (18%) had MUTYH mutations – 41 were monoallelic. Among 19 patients who had mutations in APC – 16 were APC I1307K. Only 65% (n = 159) of PV results were included in the DDx, with 35% (n = 86) of mutations not clinically suspected. Conclusions: In a diverse cohort, multiplex panel use increased genetic testing yield substantially: 35% carried pathogenic mutations in unsuspected genes, suggesting a significant contribution of expanded multiplex testing to clinical cancer risk assessment. The identification of off-target mutations broadens our understanding of cancer risk and genotype-phenotype correlations. Follow-up is ongoing to assess the clinical utility of multiplex gene panel testing. Clinical trial information: NCT02324062.
Abstract 16910: Can Spironolactone Mitigate Myocardial Fibrosis and Alter Sudden Death Risk and Heart Failure Symptoms in Patients With Hypertrophic Cardiomyopathy?: A Prospective, Randomized Trial
Authors: Martin Maron, Basavaraj Kerur, Raymond H Chan, Adam P McGraw, Xiaoying Qiao, Vikram Paruchuri, Navin Kapur, Iris Jaffe, Caitlin Harrigan, James Udelson
Journal: Circulation (2013)

Background: In hypertrophic cardiomyopathy (HCM), current therapies do not impact underlying disease pathology. Myocardial fibrosis assessed with late gadolinium enhancement (LGE) cardiovascular ma...
Individual risk factors for venous thromboembolism (VTE) in cancer patients treated with targeted therapies (TT)
Authors: B. Soini, O. Caffo, A. Ferro, G. Ambrosini, V. Murgia, F. Valduga, A. Caldara, C. Eccher, S. Tumulo, E. Galligioni
Journal: Journal of Clinical Oncology (2009)

e20549 Background: Many anticancer drugs, alone or in combination, can significantly increase the risk of VTE in cancer patients. Vascular complications however, including VTE, have emerged as a relevant toxicity also with targeted therapies (TT) (Elice, Am. J. Hematol.2008). Recently, a simple model for predicting risk of VTE in cancer patients receiving chemotherapy (CT) has been developed, based on a number of clinical and laboratory variables (Khorana, Blood 2008). In this report, we have evaluated the incidence of VTE and assessed the predictive value of the Khorana's model, in cancer patients receiving TT, alone or combined with CT. Methods: From a consecutive series of 278 patients, treated with TT ± CT between January 2006 and August 2008, we have identified for each patient the baseline values, before TT treatment, of the following variables: age, performance status, primary site of cancer, stage, comorbidities, body mass index, hemoglobin, leukocyte and platelet count and use of erythropoiesis stimulating agents. All variables have been correlated with the occurrence of VTE, at the uni- and multivariate analysis. Results: TT treatment consisted of trastuzumab in 103 patients (37%), bevacizumab in 69 (25%), cetuximab in 29 (10%), rituximab in 41 (15%), sunitinib in 16 (6%), erlotinib in 12 (4%) and sorafenib in 8 (3%). In 163 patients (59%) TT were administered concurrently with CT. In a period of 2–360 days (median 125), 14 patients (5%) developed deep vein thrombosis, complicated by pulmonary embolism in 5. None of the variables of Khorana's model has shown any significant value, in predicting VTE risk, as well as any association with different TT (i.e. bevacizumab or sunitinib) or the concomitant administration of CT. Conclusions: In our experience, the Khorana's model does not appear able to predict the risk of VTE, in patiens receiving TT treatments. Other models may be required for identifying high risk patients, who would benefit from a prophylaxis of thrombotic events. No significant financial relationships to disclose.