tbuckley/cabot-search huggingface dataset:
P0053 : Dinstict intrahepatic cytokine profiles for the differentiaton of acute cellular rejection vs recurrent hepatitis C in liver transplanted patients
Authors: P. Fytili, T. Krech, A. Gonnermann, A. Großhennig, D. Jonigk, F. Lehner, M.P. Manns, A. Koch, J.U. Becker, H. Wedemeyer
Journal: Journal of Hepatology (2015)
Abstract 14765: The Impact of Post-Procedural Intravascular Ultrasound Measured Minimum Stent Area on Mid-Term Patency After Bare Nitinol Stent and Paclitaxel-Eluting Nitinol Stent Implantation in the Superficial Femoral Artery Lesion
Authors: Kojiro Miki, Kenichi Fujii, Masashi Fukunaga, Machiko Nishimura, Ten Saita, Tetsuo Horimatsu, Hiroto Tamaru, Takahiro Imanaka, Mitsumasa Ohyanagi, Tohru Masuyama
Journal: Circulation (2013)
Determinants of HIV-1 broadly neutralizing antibody induction
Authors: Peter Rusert, Roger D Kouyos, Claus Kadelka, Hanna Ebner, Merle Schanz, Michael Huber, Dominique L Braun, Nathanael Hozé, Alexandra Scherrer, Carsten Magnus, Jacqueline Weber, Therese Uhr, Valentina Cippa, Christian W Thorball, Herbert Kuster, Matthias Cavassini, Enos Bernasconi, Matthias Hoffmann, Alexandra Calmy, Manuel Battegay, Andri Rauch, Sabine Yerly, Vincent Aubert, Thomas Klimkait, Jürg Böni, Jacques Fellay, Roland R Regoes, Huldrych F Günthard, Alexandra Trkola
Journal: Nature Medicine (2016)
Controlled bone formation using ultrasound-triggered release of BMP-2 from liposomes
Authors: Gazelle J. Crasto, Norbert Kartner, Nikita Reznik, Michael V. Spatafora, Hanje Chen, Ross Williams, Peter N. Burns, Cameron Clokie, Morris F. Manolson, Sean A.F. Peel
Journal: Journal of Controlled Release (2016)
Association of Nausea and Vomiting During Pregnancy With Pregnancy Loss
Authors: Stefanie N. Hinkle, Sunni L. Mumford, Katherine L. Grantz, Robert M. Silver, Emily M. Mitchell, Lindsey A. Sjaarda, Rose G. Radin, Neil J. Perkins, Noya Galai, Enrique F. Schisterman
Journal: JAMA Internal Medicine (2016)

Nausea and vomiting during pregnancy have been associated with a reduced risk for pregnancy loss. However, most prior studies enrolled women with clinically recognized pregnancies, thereby missing early losses.To examine the association of nausea and vomiting during pregnancy with pregnancy loss.A randomized clinical trial, Effects of Aspirin in Gestation and Reproduction, enrolled women with 1 or 2 prior pregnancy losses at 4 US clinical centers from June 15, 2007, to July 15, 2011. This secondary analysis was limited to women with a pregnancy confirmed by positive results of a human chorionic gonadotropin (hCG) test. Nausea symptoms were ascertained from daily preconception and pregnancy diaries for gestational weeks 2 to 8. From weeks 12 to 36, participants completed monthly questionnaires summarizing symptoms for the preceding 4 weeks. A week-level variable included nausea only, nausea with vomiting, or neither.Peri-implantation (hCG-detected pregnancy without ultrasonographic evidence) and clinically recognized pregnancy losses.A total of 797 women (mean [SD] age, 28.7 [4.6] years) had an hCG-confirmed pregnancy. Of these, 188 pregnancies (23.6%) ended in loss. At gestational week 2, 73 of 409 women (17.8%) reported nausea without vomiting and 11 of 409 women (2.7%), nausea with vomiting. By week 8, the proportions increased to 254 of 443 women (57.3%) and 118 of 443 women (26.6%), respectively. Hazard ratios (HRs) for nausea (0.50; 95% CI, 0.32-0.80) and nausea with vomiting (0.25; 95% CI, 0.12-0.51) were inversely associated with pregnancy loss. The associations of nausea (HR, 0.59; 95% CI, 0.29-1.20) and nausea with vomiting (HR, 0.51; 95% CI, 0.11-2.25) were similar for peri-implantation losses but were not statistically significant. Nausea (HR, 0.44; 95% CI, 0.26-0.74) and nausea with vomiting (HR, 0.20; 95% CI, 0.09-0.44) were associated with a reduced risk for clinical pregnancy loss.Among women with 1 or 2 prior pregnancy losses, nausea and vomiting were common very early in pregnancy and were associated with a reduced risk for pregnancy loss. These findings overcome prior analytic and design limitations and represent the most definitive data available to date indicating the protective association of nausea and vomiting in early pregnancy and the risk for pregnancy loss.clinicaltrials.gov Identifier: NCT00467363.
Effect of Age on Prognosis in Childhood Acute Myeloid Leukemia.
Authors: Bassem I. Razzouk, Elihu Estey, Stanley B. Pounds, Shelly Lensing, Sherry Pierce, Mark Brandt, Jeffrey E. Rubnitz, Raul C. Ribeiro, Michael Rytting, Ching-Hon Pui, Hagop M. Kantarjian, Sima C. Jeha
Journal: Blood (2004)
NF-kB Dependent Pax7 Deregulation in the Muscle Microenvaironment Promotes Wasting in Cancer Cachexia
Authors: Wei He, Emanuele Berardi, Veronica M. Cardillo, Swarnali Acharyya, Paola Aulino, Jennifer Thomas-Ahner, Jingxin Wang, Mark Bloomstom, Peter Muscarella, Peter Nau, Nilay Shah, Matthew E.R. Butchbach, Katherine Ladner, Sergio Adamo, Michael Rudnicki, Charles Keller, Dario Coletti, Federica Montanaro, Denis C. Guttridge
Journal: Nature Medicine (2012)
Is the accuracy of preoperative MRI stage in rectal carcinoma influenced by tumor height?
Authors: Laurids Østergaard Poulsen, Mette K. N. Yilmaz, Lars Oddershede, Martin Bøgsted, Gitte Holt, Mikkel Eld, Ken Ljungmann, Ursula Falkmer
Journal: Journal of Clinical Oncology (2016)

514 Background: In order to select patients with adenocarcinoma of the rectum (RC) for optimal treatment strategies, there is a need for accurate staging of the neoplastic disease. Here, magnetic resonance imaging (MRI) is considered to be the gold standard. However, some concerns have been raised about the reproducibility of earlier results. Newer treatment strategies which include organ saving in RC patients will further emphasize the need. The aim of the present study was to evaluate the degree of accuracy of the MRI staging. Methods: All patients diagnosed with RC in northern Denmark 2009-2013 (n = 1017) were screened for inclusion. All MRI were performed on 1.5 T MRI scanners and the evaluations were made by in all four expert GI-radiologists. Only patients who were offered surgery without preoperative treatment were included (n = 357). The result of the preoperative MRI staging was correlated to the postoperative histopathological stage. Results: There were 56, 131 and 190 patients respectively with low- (0-5 cm from the anal verge), mid- (5-10 cm) and high RC (10-15 cm). MRI T-staging was in accordance with the histopathology in 84 % of the cases (81% for low, 86% for mid, and 83% for high tumors, respectively) and the accuracy was not affected by tumor height. The results were consistent over time. Concerning the MRI staging of nodal-involvement, there was a sensitivity of 88% and a specificity of 30%. Data regarding tumor invasion and distance from the tumor to mesorectal fascia will be presented at the meeting. Conclusions: MRI T-stage correlated well with postoperative histopathological T-stage, whereas the correlation to nodal involvement was poor and in accordance with previous results.
Vitamin D, vitamin A, the primary melanoma transcriptome and survival
Authors: S.J. O'Shea, J.R. Davies, J.A. Newton-Bishop
Journal: British Journal of Dermatology (2016)

Survival from melanoma is influenced by several, well‐established clinical and histopathological factors, e.g. age, Breslow thickness and microscopic ulceration. We (the Section of Epidemiology and Biostatistics, University of Leeds) have carried out research to better understand the biological basis for these observations. Preliminary results indicated a protective role for vitamin D in melanoma relapse and that higher vitamin D was associated with thinner primary melanomas. Funding from the British Skin Foundation enabled JNB to establish a study of the effects of vitamin A in melanoma. The results suggested that vitamin A could reduce the protective effect of vitamin D in terms of overall survival. Therefore, we propose that vitamin D3 supplementation alone might be preferable to combined multivitamin preparations, where vitamin D supplementation is deemed to be appropriate. Proving a causal link between vitamin D and melanoma‐specific survival is challenging. We have shown limited evidence of causation in a Mendelian randomization experiment (described in more detail later). Recent work in Leeds has also shown that higher vitamin D may be protective for microscopic ulceration. Taken together, vitamin D appears to be associated with less aggressive primary melanomas and may itself influence outcome. We continue to explore the role of vitamin D in melanoma survival and the optimum levels that might be crucial.
A randomized phase III study of vinflunine versus an alkylating agent of physician’s choice in metastatic breast cancer (MBC) previously treated with or resistant to an anthracycline, a taxane, an antimetabolite and a vinca-alkaloid.
Authors: Javier Cortes, Christelle Levy, Yuri Demidchik, Laslo Roman, Hugues Pierre Bourgeois, Corinne Veyret, Simon Spazzapan, Jean-Marc Ferrero, Ta-Chung Chao, Yauheniya Karchmit, Marc Espie, Jean-Marc A. Nabholtz, Xavier Gonzalez, Vasili Beliakouski, Mario Campone
Journal: Journal of Clinical Oncology (2015)

1031 Background: There is currently no consensus on the efficacy of chemotherapy (CT) beyond 3rd line in MBC and only eribulin (which has been recently approved) has shown to improve survival. No proven treatment options are available. VFL was tested in comparison with an AA of physician’s choice in MBC treated in > 3rdline. Methods: This open-label phase 3 study enrolled 594 MBC pts who have received at least 2 prior CT regimens for MBC including an anthracycline (A), a taxane (T), an antimetabolite (AM) and a vinca-alkaloid (VA). Pts were no longer candidate for those CT because of resistance and/or intolerance. Pts were randomised to VFL 280 mg/m² every 3 w (N=298) or to an AA used as a single agent every 3 w (N=296). Randomization was stratified by performance status (PS), number of prior CT lines for MBC and disease measurability. Primary endpoint was OS population assuming a median OS of 6.5 m for AA and a 2 m difference between arms. Results: Pts had a median age of 58 y [range: 28-79]; visceral metastases for 81.5% them; and had received a median of 4 prior CT regimens for MBC. Resistance was the main reason for no retreatment with A (59.9%), T (82.5%), AM (93.3%) and VA (87.4%). In the AA arm, the most frequently used agents were cyclophosphamide (33.4% of pts), carboplatin (31.4%) and cisplatin (15.5%). Median OS did not differ between arms: 9.1 m for VFL and 9.3 m for AA. Response rates were similar for VFL (6.4%) and for AA (4.4%); disease control rate was higher for VFL than for AA (43.6% vs 35.5%, P=0.0424). Median PFS was 2.4 m for VFL and 1.9 m for AA (P=0.4927). For VFL, the main grade 3-4 drug related adverse events were neutropenia (19.2% of pts vs 10.8% for AA) rarely complicated (0.7% of febrile neutropenia and 2% of neutropenic infection) and asthenia/fatigue (10.8% with grade 3; no grade 4). For AA, they were thrombocytopenia (7.7% of pts vs 3% for VFL) and asthenia/fatigue (3.1% of grade 3 only). Conclusions: VFL 280 mg/m² every 3 w did not improve OS compared to an AA of physician’s choice in MBC pts treated in > 3rd line. The safety profile of VFL was acceptable and allows to consider testing VFL at 320 mg/m². Clinical trial information: NCT01091168.
Early operable primary breast cancer in elderly (≥70 years) women: Are they biologically different from their younger counterparts?
Authors: K. Cheung, B. M. Syed, A. R. Green, D. A. Morgan, I. O. Ellis
Journal: Journal of Clinical Oncology (2010)

10547 Background: Biological features of breast cancer seem to change with age. Most studies have small sample size or data collected from multiple centres with different laboratory protocols limiting their importance. This study was part of an ongoing research programme on breast cancer in the elderly, and was conducted in a single breast unit with a dedicated breast histopathology research team. Methods: Over 36 years (1973-2008), 2,000+ elderly (≥70 years) women with early operable primary breast cancer were managed in our dedicated elderly primary breast cancer clinic. Of these 831 underwent surgery as primary therapy and 575 had good quality tumour samples available for tissue microarray (TMA) analysis using indirect immunohistochemistry. A total of 15 biomarkers were measured using pre-defined cut-offs: ≥1% of cells stained considered positive in ER, PR, HER4 and E-Cadherin, ≥5% in p53, ≥10% in CK (5/6, 7/8, 14, 17, 18 and 19), BRCA1, Ki67 and MUC1; HER2 with 3+ score was considered positive. The results were compared with those from a previously characterised, consecutive series (N=1,809) of younger (<70 years) patients with early operable primary breast cancer treated in the same unit between 1986 – 1998. Results: The expression of ER (p<0.001), HER4 (p<0.000), CK14 (p<0.000), CK17 (p<0.02), CK18 (p<0.000) and p53 (p<0.000) increased with advancing age, while the reverse was seen with CK 7/8 (p<0.002), Ki67 (p<0.000), BRCA1 (p<0.000) and E-Cadherin (p<0.000). No change with age was seen in all other biomarkers. Conclusions: The biology of breast cancer appears to change with age, with clear trend seen in a significant number of biomarkers. The pattern is consistent with reduced aggressiveness of the disease with advancing age as shown by increasing expression of ER and cell differentiation markers, and decreasing expression of proliferation markers. This would have potential impact on clinical management and outcome. No significant financial relationships to disclose.
Biomarkers of Response and Resistance to DNA Repair Targeted Therapies
Authors: Elizabeth H. Stover, Panagiotis A. Konstantinopoulos, Ursula A. Matulonis, Elizabeth M. Swisher
Journal: Clinical Cancer Research (2016)

Drugs targeting DNA damage repair (DDR) pathways are exciting new agents in cancer therapy. Many of these drugs exhibit synthetic lethality with defects in DNA repair in cancer cells. For example, ovarian cancers with impaired homologous recombination DNA repair show increased sensitivity to poly(ADP-ribose) polymerase (PARP) inhibitors. Understanding the activity of different DNA repair pathways in individual tumors, and the correlations between DNA repair function and drug response, will be critical to patient selection for DNA repair targeted agents. Genomic and functional assays of DNA repair pathway activity are being investigated as potential biomarkers of response to targeted therapies. Furthermore, alterations in DNA repair function generate resistance to DNA repair targeted agents, and DNA repair states may predict intrinsic or acquired drug resistance. In this review, we provide an overview of DNA repair targeted agents currently in clinical trials and the emerging biomarkers of response and resistance to these agents: genetic and genomic analysis of DDR pathways, genomic signatures of mutational processes, expression of DNA repair proteins, and functional assays for DNA repair capacity. We review biomarkers that may predict response to selected DNA repair targeted agents, including PARP inhibitors, inhibitors of the DNA damage sensors ATM and ATR, and inhibitors of nonhomologous end joining. Finally, we introduce emerging categories of drugs targeting DDR and new strategies for integrating DNA repair targeted therapies into clinical practice, including combination regimens. Generating and validating robust biomarkers will optimize the efficacy of DNA repair targeted therapies and maximize their impact on cancer treatment. Clin Cancer Res; 22(23); 5651-60. ©2016 AACR.
Anthracycline-related cardiomyopathy in childhood cancer survivors and association with polymorphisms in the carbonyl reductase genes: A Children's Oncology Group study.
Authors: J. G. Blanco, C. Sun, W. Landier, L. Chen, K. C. Oeffinger, M. M. Hudson, J. P. Neglia, A. K. Ritchey, M. V. Relling, S. Bhatia
Journal: Journal of Clinical Oncology (2010)

9512 Background: Anthracycline-related cardiomyopathy is a well-recognized dose-limiting complication. Inter-individual variability in risk exists, potentially due to genetic susceptibility. Carbonyl reductases (CBR) catalyze reduction of anthracyclines to cardiotoxic alcohol metabolites. Polymorphisms in CBR3 V244M and CBR1 G1096A impact CBR activity. We examined the role of functional polymorphisms in CBR3 and CBR1 on risk of cardiomyopathy. Methods: Using a case-control design, 165 cases with documented cardiomyopathy and 323 controls (cancer survivors with no cardiomyopathy; matched on primary diagnosis, follow-up, race/ethnicity) provided germline DNA. Therapeutic exposures were summarized. Results: Primary diagnoses included acute leukemia (164), lymphoma (111), sarcoma (120) and others (93); 51% were females; 77% whites; median age at cancer diagnosis: 7.5 years; time to cardiomyopathy: 7.1 years; median anthracycline dose – cases: 300mg/m2; controls: 140mg/m2. Multivariate analysis revealed anthracycline dose (per 100mg/m2: OR=1.8, p<0.001), and chest radiation (OR=3.13, p=0.05) to be associated with cardiomyopathy. The role of polymorphisms in CBR3/CBR1 was then examined, adjusting for chest radiation. There was a borderline association between CBR3 V244M and cardiomyopathy (OR=1.5, p=0.08 for GG vs. GA/A); and no association for CBR1 G1096A (OR=1.0, p=0.9). However, upon stratification by anthracycline does, the association with CBR3 V244M became stronger among subjects exposed to ≤250mg/m2 (OR=6.4, p=0.006), but disappeared for those exposed to >250mg/m2 (OR=0.9, p=0.8). Similar but non-significant associations were observed for CBR1 (OR=3.3, p=0.10; OR=0.8, p=0.7, respectively). Conclusions: Using the largest cohort of documented cardiomyopathy, this report demonstrates a clear dose-response relation between anthracyclines and cardiomyopathy, and selectively greater impact of CBR3 on risk of cardiomyopathy after low-dose anthracycline exposure. These data identify a definable subset of patients that may benefit from cardioprotection, surveillance or pharmacologic interventions. No significant financial relationships to disclose.
Management of Systemic Lupus Erythematosus During Pregnancy
Authors: Lisa R. Sammaritano
Journal: Annual Review of Medicine (2016)

Reproductive issues including contraception, fertility, and pregnancy are important components of the comprehensive care of women with systemic lupus erythematosus (SLE). SLE pregnancies are complicated due to risk for maternal disease exacerbation and potential for fetal and neonatal complications. Pre-pregnancy assessment is important to identify patients with severe disease-related damage who should avoid pregnancy, counsel patients to conceive when disease has been stable and inactive on appropriate medications, and assess relevant risk factors including renal disease, antiphospholipid antibody, and anti-Ro/SS-A and anti-La/SS-B antibodies. With careful planning, monitoring, and care, most women with SLE can anticipate a successful pregnancy.
A randomized, parallel-arm, phase II trial to assess the efficacy of preoperative ixabepilone with or without cetuximab in patients with triple-negative breast cancer (TNBC).
Authors: Angel Augusto Rodriguez, Nina Salazar, Tejal Amar Patel, Jaime Alberto Mejia, Amber Froehlich, Nour Sneige, Sapna Amin, Heidi Weiss, Edgardo Rivera, Jenny Chee Ning Chang
Journal: Journal of Clinical Oncology (2014)

1133 Background: Epithelial growth factor receptor pathway (EGFR) is expressed in TNBC and may be important in a subset of this heterogeneous disease. We evaluated the efficacy and toxicity of an anti-EGFR antibody (cetuximab) combined with ixabepilone given to the TNBC patients (pts) in the neoadjuvant setting. This study was designed to detect an increase in pathological complete response (pCR) rate, defined as no residual disease in the breast, from 20% to 40% in each arm, using a Simon optimal two stage design, with one-sided alpha=10% and power=80%. At least three responses out of 12 patients were needed to proceed with second stage for each arm. Methods: All pts received 4 cycles of preoperative ixabepilone 40 mg/m2 every 3 weeks. In addition, patients were randomized to receive either 12 infusions of weekly cetuximab (400mg/m2 on week 1, then 250 mg/m2) or not. Race, proliferation rate, and TILs was correlated with pCR. Results: To date, a total of36 pts with stage II-IIIA TNBC were enrolled. Median age was 54 years (range 35-79 years) with median tumor size of 6.1 cm (range 2-18 cm). The median proliferation rate (Ki-67) was 67.2% (range 8%-95%). Pts were Hispanic (36%), White (39%), African-American (19%) and others (6%). In ixabepilone alone arm, pCR was observed in only 14.3%, and this monotherapy arm did not progress to second stage. To date, pCR was observed in 31.3% in ixabepilone/cetuximab arm, with 6 patients still on treatment. Adverse events for the combination arm were modest, mainly grade 1-2 (neutropenia: 4%, skin: 83 %, GI: 50 %, fatigue: 100 %). Grade 3 febrile neutropenia in 3 % were observed. No statistically significant correlation with race, Ki67, and TILs with pCR rate was observed. Conclusions: The addition of cetuximab to ixabepilone may improve the rate of pathological complete response in TNBC pts. There was no association between race or proliferation and response to ixabepilone and cetuximab. Evaluation of EGFR, p-EGFR and EGFR pathway -associated genes, PTEN, mutational analysis of PI3K/mTOR pathway and next generation genomic analysis is underway to evaluate for potential predictive biomarkers of response to EGFR inhibition. Clinical trial information: NCT01097642.
David Oliver: Frailty in acute care
Authors: David Oliver
Journal: BMJ (2016)

The National Institute for Health and Care Excellence recently published guidelines on assessing and managing patients with multimorbidity.1 2 These placed distinct and welcome emphasis on frailty—adding momentum to several recent, professionally led good practice resources and guidelines explicitly highlighting the importance of frailty in community and acute care and showcasing services that work.3 4 5 6 7 8

Much nuanced research has been published on frailty as a clinical and physiological entity.9 10 11 It’s increasingly prevalent with older age but can affect people in their 50s. To oversimplify: two large schools of …