tbuckley/cabot-search huggingface dataset:
A pilot study of palbociclib in patients with HER2-positive breast cancer with brain metastasis.
Authors: Cesar Augusto Santa-Maria, Priya Kumthekar, Alfred Rademaker, Leeaht Gross, Sarika Jain, Lisa E. Flaum, William John Gradishar, Massimo Cristofanilli
Journal: Journal of Clinical Oncology (2017)

TPS1110 Background: HER2+ breast cancers have the propensity to metastasize to the CNS. Most systemic therapy does not cross the blood-brain barrier (BBB) effectively, limiting treatment options. Palbociclib is a small molecule inhibitor of cyclin dependent kinases (CDK) 4 and 6, which has been studied in hormone positive breast cancers and found to have significant anti-tumor activity. Preclinical models demonstrate HER2+ tumors require cyclin D1 and CDK4 for progression and maintenance, and palbociclib has been found to have single agent activity in transgenic HER2+ models. Preclinical studies have also found that palbociclib crosses the BBB and exerts anti-cancer effects; indeed, clinical trials investigating its activity in primary brain tumors are ongoing. The summary of these data provide rationale for investigation of palbociclib in patients with HER2+ breast cancer and brain metastasis. Methods: A single arm study of palbociclib in patients with metastatic HER2+ breast cancer with brain metastasis was designed. The primary objective is to determine overall radiographic response rate in the CNS using modified RANO-BM criteria. Secondary objectives include PFS, OS, systemic response rates, safety, and tolerability. Exploratory objectives include assessment of mutational profiles in tissue and ctDNA, and quality of life endpoints using FACT-Cog and FACT-Br. Eligible patients must have metastatic HER2+ breast cancer with measurable brain metastasis (at least 1 lesion &gt; = 5mm). Patients with rapidly progressive symptoms or with leptomeningeal disease are excluded. Concurrent therapy with trastuzumab is allowed. Eligible patients are treated with palbociclib 125mg PO (21 days on, 7 days off) until progressive disease or unacceptable toxicity. Available archival tissue will be obtained, ctDNA/FACT-Cog/Br will be assessed at baseline, 2, and 4 months. A total of 20 patients will be enrolled. To detect a radiographic response rates increase from 23% to 40%, a Bayesian posterior probability will be calculated after the response status in 20 patients has been assessed. The goal is that there is at least an 80% probability that the response rate exceeds 40%. Clinical trial information: NCT02774681.
Correction
Authors: Stephen J. Polyak, Chihiro Morishima, Roy Hawke
Journal: Hepatology (2008)

In the letter to the editor “Antiviral effects of silymarin against hepatitis C: The jury is still out” (HEPATOLOGY 2008;48:345-346; DOI: 10.1002/hep.22235), the author affiliations are corrected below.
Abstract 308: An in vitro Model of Cardiac Stem Cell Therapy to Study the Coupling of Primary and Stem Cell-derived Cardiomyocytes
Authors: Francesco S Pasqualini, Yvonne Aratyn-Schaus, Hongyan Yuan, Megan L McCain, George J Ye, Sean P Sheehy, Patrick H Campbell, Kevin K Parker
Journal: Circulation Research (2015)

For cardiac cell therapy to be effective, newly formed immature cardiomyocytes need to structurally and functionally integrate with the existing myocardium. Unfortunately, testing the electro-chemo-mechanical coupling of mature and immature cardiomyocytes in vivo is difficult. Here we engineered two cell μtissues containing combinations of mouse neonate, ES-derived, and iPS-derived cardiac myocytes on flexible substrates and utilized ratiometric calcium detection and traction force microscopy to measure excitation-contraction coupling in individual cells and in the pairs. We found that SC-derived cardiac myocytes can structurally couple with neonate cardiomyocytes to functionally support synchronous contraction, yet diastolic calcium levels were reduced in SC-derived cardiomyocytes. Consistently, neonate cardiomyocytes exerted peak systolic forces that were ~1.5-fold higher than that generated by SC-derived myocytes, yielding an imbalance in tension within the pair that was dissipated by focal adhesion-like structures at the cell-cell boundary. Finally we developed a finite element model of two-cell tissue contraction to demonstrate that an imbalance in isometric tension is sufficient to limit force transmission across cell-cell boundaries. Taken together, these results suggest that reduced force transmission between poorly coupled immature and native cardiomyocytes may explain the incomplete repair of ejection fraction observed in several clinical studies of cardiac cell therapy.
Serum microcystin levels positively linked with risk of hepatocellular carcinoma: A case‐control study in southwest China
Authors: Chuanfen Zheng, Hui Zeng, Hui Lin, Jia Wang, Xiaobin Feng, Zhiqun Qiu, Ji‐an Chen, Jiaohua Luo, Yang Luo, Yujing Huang, Lingqiao Wang, Wenyi Liu, Yao Tan, Anwei Xu, Yuan Yao, Weiqun Shu
Journal: Hepatology (2017)

Microcystins have been reported to be carcinogenic by animal and cell experimentation, but there are no data on the linkage between serum microcystins and hepatocellular carcinoma (HCC) risk in humans. We conducted a clinical case-control study to investigate the association between serum microcystins and HCC risk after controlling several known risk factors, such as hepatitis B virus, alcohol, and aflatoxin. From December 2013 to May 2016, 214 patients newly diagnosed with HCC along with 214 controls (frequency-matched by age and sex) were recruited from three hospitals in Chongqing, southwest China. Basic information on lifestyle and history of disease was obtained by questionnaire. Blood samples were collected and analyzed for serum microcystin-LR (MC-LR) and aflatoxin-albumin adduct by enzyme-linked immunosorbent assay and for hepatitis B surface antigen status by chemiluminescence assay. Binary logistic regression analyses were performed to assess the independent effects of MC-LR and its joint effects with other factors on HCC risk. The adjusted odds ratio for HCC risk by serum MC-LR was 2.9 (95% confidence interval [CI], 1.5-5.5) in all patients. Notably, a clear relationship between increased MC-LR level (Q2, Q3, and Q4) and HCC risk was observed with elevated adjusted odds ratios (1.3, 2.6, and 4.0, respectively). Positive interactions with the additive model were investigated between MC-LR and hepatitis B virus infection (synergism index = 3.0; 95% CI, 2.0-4.5) and between MC-LR and alcohol (synergism index = 4.0; 95% CI, 1.7-9.5), while a negative interaction was found between MC-LR and aflatoxin (synergism index = 0.4; 95% CI, 0.3-0.7). Additionally, serum MC-LR was significantly associated with tumor differentiation (r = -0.228, P < 0.001).We provide evidence that serum MC-LR was an independent risk factor for HCC in humans, with an obvious positive interaction with hepatitis B virus and alcohol but a negative interaction with aflatoxin. (Hepatology 2017;66:1519-1528).
Impact of Mild to Severe Hemophilia B on Quality of Life Including Pain and Functional Abilities in Affected Men/Women and Caregivers of Affected Boys/Girls: Analysis of Patient Reported Outcomes in the Bridging Hemophilia B Experiences Results and Opportunities into Solutions (B-HERO-S) Study
Authors: Tyler W. Buckner, Michelle Witkop, Christine Guelcher, Robert F. Sidonio, Christopher E. Walsh, Craig M. Kessler, David Clark, Wendy E. Owens, Neil Frick, Neeraj N Iyer, David L Cooper
Journal: Blood (2016)
Which patient characteristics drive treatment decisions in elderly patients with early stage hormone receptor–positive breast cancer?
Authors: Sacha Satram-Hoang, Carolina M. Reyes, Alisha Stein, Khang Q. Hoang, Faiyaz Momin, Patricia Cortazar
Journal: Journal of Clinical Oncology (2017)

538 Background: Hormone receptor positive (HR+), human epidermal growth factor receptor 2 negative (HER2-) is the most common biologic subtype of breast cancer (BC). We examined treatment patterns and outcomes associated with adjuvant or neoadjuvant therapy among elderly patients (pts) in the US. Methods: The analysis included 18,470 first primary HR+HER2- BC pts from the linked SEER-Medicare database. Pts were diagnosed with Stage I-III disease between 1/1/2007-12/31/2011, ≥66 years, continuously enrolled in Medicare Parts A/B in the year prior to diagnosis, enrolled in Part D in the year after diagnosis, and underwent BC surgery ≤6 months after diagnosis. Time-varying Cox proportional hazards regression assessed overall survival adjusting for pt characteristics. Date of last follow-up was 12/31/2013. Results: There were 13,670 (74%) pts treated with hormonal therapy +/- chemotherapy and 4,800 (26%) untreated. Compared to treated pts, untreated pts were older, had earlier stage, lower grade, smaller tumors, poorer performance, higher comorbidity, and less genomic testing for risk of recurrence (p&lt;0.0001). In a multivariate analysis, increasing age, stage, tumor size, tumor grade, comorbidity score and poor performance were significantly associated with higher mortality risks, while use of genomic testing was associated with a lower risk of death. The Cox model showed a 48% higher risk of death in untreated compared to treated pts (HR=1.48; 95% CI=1.35-1.61). Even in a subset of 8,967 pts with stage I disease, tumor size &lt;2.0cm and grade 1/2; untreated pts had a 22% higher risk of death compared to treated pts (HR=1.22; 95% CI=1.05-1.41). Conclusions: Patients who are older with favorable disease characteristics (earlier stage, smaller tumor, lower grade) are less likely to be treated and have a higher risk of death compared to pts who received adjuvant or neoadjuvant therapy. The unmet need among elderly BC pts remains, suggesting that age should not deter guideline-based therapy. [Table: see text]
Obesity-Related Changes in Cardiac Structure and Function Among Asian Men and Women
Authors: Yau-Huei Lai, Ming-En Liu, Cheng-Huang Su, Chun-Ho Yun, Chia-Yuan Liu, Charles Jia-Yin Hou, Kuang-Chun Hu, Chung-Lieh Hung, Hung-I Yeh, Carolyn S.P. Lam
Journal: Journal of the American College of Cardiology (2017)
Phase 3 randomized study of adjuvant anastrozole (A), exemestane (E), or letrozole (L) with or without tamoxifen (T) in postmenopausal women with hormone-responsive (HR) breast cancer: The FATA-GIM3 trial.
Authors: Francesco Perrone, Ciro Gallo, Michele De Laurentiis, Giancarlo Bisagni, Grazia Arpino, Maria Giuseppa Sarobba, Ferdinando Riccardi, Antonio Russo, Lucia Del Mastro, Alessio Aligi Cogoni, Francesco Cognetti, Stefania Gori, Antonio Frassoldati, Domenico Amoroso, Lucio Laudadio, Luca Moscetti, Filippo Montemurro, Francesco Nuzzo, Paolo Carlini, Sabino De Placido
Journal: Journal of Clinical Oncology (2017)

515 Background: Uncertainty still exists regarding the optimal schedule of adjuvant treatment of breast cancer with aromatase inhibitors (AI) and no trial has ever compared all the three AI. Methods: FATA-GIM3 is a multicenter, open label, 2x3 factorial phase 3 randomized study of adjuvant A, E and L upfront (UP - for 5 years) or sequentially (SEQ - for 3 years after 2 years of T) in postmenopausal HR breast cancer pts. Two comparisons were planned: UP vs SEQ and A vs E vs L. DFS (including local or distant relapse, second breast or non-breast cancer, DCIS and death, whichever came first) was the primary end-point; 2% at 5 yrs (corresponding to a HR of 0.79) was defined as the minimum difference required to declare superiority of UP vs SEQ. With two-tailed alfa 0.05, power 80%, 669 events and the enrolment of 3600 patients were planned. Following Data Monitoring Committee advice, final analysis was performed after 5yrs median follow-up. For each comparison a Cox regression model was applied adjusted by stratification factors and stratified by the other treatment factor. Analyses were based on intention-to-treat. Results: from 3/2007 to 7/2012, 3697 patients were enrolled at 76 centres. Median age 64, pT1 69.7% , pN0 64.3%, ER and PgR positive 88.9%, HER2 positive 8.9%, previous chemotherapy 38.3%. At 60 months median follow-up, 401 events were reported. 5yrs DFS was 89.8 with UP and 88.5 with SEQ (delta 1.32%, 95% CI -0.90-3.54; HR 0.89, 95% CI 0.73-1.08; P=0.23). 5yrs DFS was 90.0 with A, 88.0 with E and 89.4 with L (P=0.19). Conclusions: in the FATA-GIM3 trial there is a small non statistically significant DFS advantage for UP vs SEQ. No significant difference is evident among the three AI. Supported by the FARM5K3MEE AIFA grant from the Italian Drug Agency. Clinical trial information: NCT00541086.
The Effect of Positive SWOG Treatment Trials on Survival of Patients With Cancer in the US Population
Authors: Joseph M. Unger, Michael LeBlanc, Charles D. Blanke
Journal: JAMA Oncology (2017)

Recently, tremendous prominence has been given to the investigation of the effect of different research processes as part of the Cancer Moonshot. More than half a century ago, the National Cancer Institute (NCI) established a network of publicly funded cancer cooperative research groups to systematically evaluate new treatments for efficacy and safety.To examine the extent to which positive NCI-sponsored cancer treatment trials have benefited patients with cancer in the US population.This investigation used study data from SWOG, an NCI-sponsored network cooperative research group. All treatment trials during SWOG's 60-year history (1956-2016) were identified for which the new, experimental therapy provided a statistically significant improvement in overall survival. It was assumed that the new, proven treatments from these trials established new standards for cancer care in the treatment community. Twenty-three positive SWOG treatment trials were identified from a variety of different disease settings.This study estimated population life-years gained from the 23 treatment trials through 2015 by mapping the effect of the new treatments onto the US cancer population using an area under the Kaplan-Meier survival curve approach that combined trial-specific hazard function and hazard ratio results, along with Surveillance, Epidemiology, and End Results program and life table data. Calculations were age adjusted. The US dollar return on investment was estimated as the ratio of the total investment by the NCI in the treatment trial program divided by the estimate of life-years gained.In total, 12 361 patients were enrolled to the 23 positive trials from 1965 to 2012. The study estimated that 3.34 million (95% confidence limit, 2.39-4.15 million) life-years were gained from these 23 trials through 2015. Estimates were greater than 2 million life-years gained under most model simulations. The US dollar return on investment was $125 per life-year gained.SWOG treatment trials have had a substantial impact on population survival for patients with cancer over 60 years. The NCI's investment in its cancer cooperative group research program has provided exceptional value and benefit to the American public through its research programs generating positive cancer treatment trials.clinicaltrials.gov Identifiers: NCT00004001, NCT00075764, and NCT00644228.
St. John's Hospital for Diseases of the Skin
Authors: T. Robinson, C. M. Campbell, N. W. Bourns
Journal: BMJ (1887)

The annual general meeting of the governors of this insti- tution was held last week at the Criterion, about 70 people being present.Considerable interest attached to the proceedings in consequence of the undesirable notoriety the hospital has recently attained, owing to the attacks made in the Press against the secretary, and the actions-at-law which followed.At half-past three a decided struggle commenced, and it was evident enough that two factions were present.Colonel Mercier was proposed to the chair, but an amendment was immediately tabled in favour of the Earl of Aberdeen.His lordship, though denying any feeling of prejudice, was evidently inclined to side with a compaot and vigorous band of medical and other gentlemen who sat together, and were referred to several times as "the opposition."Colonel Mercier expressed the hope that as the charges against the secretary had resulted in a verdict in his favour, nothing further would be heard from those who were at one time pressing for an enquiry, although, when it was proposed that there should be a committee of enquiry, they had postponed it.It was proposed to recommend that
Disparities in multigene signature testing and its impact on adjuvant therapy in early stage breast cancer.
Authors: Maris S. Jones, Melanie Goldfarb, Mansen Wang, Emily Ho
Journal: Journal of Clinical Oncology (2017)

550 Background: Commercially available prognostic multigene signature tests (PMT) have been available for over a decade to guide adjuvant therapy in early stage breast cancer. This study explores persistent disparities in the availability of PMT and how results influence the use of adjuvant therapy. Methods: Females &gt; 18 years of age with newly diagnosed, primary, Stage I-III, ER positive, HER2-neu negative breast cancer that did not receive neoadjuvant therapy between 2006-2014 were captured from the National Cancer Database (NCDB) participant user file. Univariate and multivariate analyses identified factors associated with utilization of PMT as well as receipt of adjuvant chemotherapy for patients with PMT risk stratification. Results: Of 574,921 eligible females, 130,297 (22.66%) received PMT. Almost all patients that had PMT had pathologically negative (pN0 = 83%) or 1-3 positive LNs (pN1 = 16%). Controlling for tumor features, patients least likely to have PMT were of lower socioeconomic status, uninsured, not White non-Hispanic, &lt; 40 or &gt; 70 years of age, and treated at community hospitals or in the Western region (all p &lt; 0.001). Very few patients with PMT results actually received adjuvant chemotherapy (0.64% of 92,235). Of this small group, younger patients (ages 18-49) those with less education (OR = 1.37, 95%CI:1.07-1.76), positive lymph nodes, and larger tumors (OR = 1.62, 95%CI:1.37-1.91) were more likely to receive adjuvant chemotherapy whereas patients with PR positive tumors (OR = 0.33, 95%CI:0.18-0.60) and those treated at academic facilities (OR = 0.81, 95%CI:0.68-0.96) were less likely to receive adjuvant chemotherapy after controlling for competing factors. Intermediate (OR = 5.34, 95%CI: 4.42-6.45) or high risk (OR = 32.65, 95%CI: 25.74-41.43) PMT scores had the greatest impact on receipt of adjuvant chemotherapy regardless of nodal status. Conclusions: Common socioeconomic and racial/ethnic disparities exist for PMT testing, though inappropriate use (high T or N stage) was minimal. Since PMT results strongly influenced recommendation of adjuvant therapy, decreasing disparities and making PMT available to all patients that are deciding on adjuvant therapy should be a priority.
Rest tremor revisited: Parkinson’s disease and other disorders
Authors: Wei Chen, Franziska Hopfner, Jos Steffen Becktepe, Günther Deuschl
Journal: Translational Neurodegeneration (2017)

Tremor is the most common movement disorder characterized by a rhythmical, involuntary oscillatory movement of a body part. Since distinct diseases can cause similar tremor manifestations and vice-versa, it is challenging to make an accurate diagnosis. This applies particularly for tremor at rest. This entity was only rarely studied in the past, although a multitude of clinical studies on prevalence and clinical features of tremor in Parkinson's disease (PD), essential tremor and dystonia, have been carried out. Monosymptomatic rest tremor has been further separated from tremor-dominated PD. Rest tremor is also found in dystonic tremor, essential tremor with a rest component, Holmes tremor and a few even rarer conditions. Dopamine transporter imaging and several electrophysiological methods provide additional clues for tremor differential diagnosis. New evidence from neuroimaging and electrophysiological studies has broadened our knowledge on the pathophysiology of Parkinsonian and non-Parkinsonian tremor. Large cohort studies are warranted in future to explore the nature course and biological basis of tremor in common tremor related disorders.
An Adapted Gating Strategy Integrating a Myelomonocytic Window Is Necessary For Correct Flow Cytometric Diagnosis In a Large Proportion Of AML With Mutated NPM1
Authors: Miriam Kull, Christian Langer, Michela Tassara, Christine Schoepflin, Olena Bayer, Carina Morlok, Andrea Kündgen, Helmut R. Salih, Thomas Kindler, Heinz-August Horst, Michael Lübbert, Hans Salwender, Katharina Götze, Felicitas Thol, Arnold Ganser, Peter Paschka, Verena I. Gaidzik, Konstanze Döhner, Hartmut Döhner, Richard F. Schlenk, Michaela Feuring-Buske
Journal: Blood (2013)
Targeting epithelial-mesenchymal transition: Metal organic network nano-complexes for preventing tumor metastasis
Authors: Jin-Xuan Fan, Di-Wei Zheng, Lei Rong, Jing-Yi Zhu, Sheng Hong, Cao Li, Zu-Shun Xu, Si-Xue Cheng, Xian-Zheng Zhang
Journal: Biomaterials (2017)
Yoga in women undergoing treatment for breast cancer: Impact on quality of life in a randomized controlled trial.
Authors: Nita S. Nair, Nishu Singh Goel, Rohini W Hawaldar, Shabina Siddique, Vani Parmar, Aarti Pandey, Rajendra A. Badwe
Journal: Journal of Clinical Oncology (2017)

527 Background: Yoga has been tested in multiple small-randomized studies for its impact on quality of life (QOL) on breast cancer (BC). We propose to study the effect of yoga on disease free survival as the primary endpoint in women with operable breast cancer. (Study methodology details refer to NCT02161900). Methods: Women with non-metastatic BC were randomized to yoga and conventional exercise (YCE) versus conventional exercise only (CE) in addition to standard therapy. Over and above documentation of recurrence and death, QOL was assessed in these women using the EORTC QLQC30, BR23, Brief fatigue inventory (BFI), Visual pain scores (VPS) and a spirituality questionnaire (SQ). EORTC QLQ was assessed at baseline (BL), 6-9 months (mo), 18-21 mo. BFI and VPS at BL, 6-8 mo and 12-15 mo and SQ at BL and 12-15 mo. We report the first interim analysis of QOL in 605 patients randomized to the study with atleast 1 year of follow up. The groups were balanced in both arms with respect to clinico-pathological factors. Results: At 6-9 mo (completion of adjuvant therapy), there was no significant difference in global QOL scores (p = 0.08), however 52% women on YCE showed an improvement from baseline compared to 42% in CE. At 18-21 mo emotional function scores were better in YCE (p = 0.002); with lesser systemic side effects in YCE arm (44% vs 56% p = NS). The median score of fatigue after adjuvant therapy measured by QLQ C30 was lower in YCE (17.37vs22.22, p = 0.003) which was similar to that observed by BFI at 12-15 mo (1.6vs 2, p = 0.04). Also in YCE there was lower reporting of detriment in general activity (41%vs 59%) and mood (34%vs66%) (p = NS). In VPS at 12-15mo, the median scores for pain intensity (p = 0.042), pain on movement (p = 0.038), pain on mobilization (p = 0.008) were lower in YCE. Lastly SQ assessed spirituality and showed no difference, but less deterioration compared to baseline scores in YCE. Conclusions: Yoga did not show a significant difference in global QOL but had a major benefit reaching statistical significance in fatigue, emotional score and pain. Yoga is a low-risk, low-cost complementary therapy that may improve compliance to therapy by improving parameters that can affect day-to-day activity in women with breast cancer. Clinical trial information: NCT02161900.
Patient‐reported outcomes in the <scp>SOluble</scp> guanylate Cyclase <scp>stimulatoR</scp> in <scp>heArT failurE patientS</scp> with <scp>PRESERVED</scp> ejection fraction (<scp>SOCRATES‐PRESERVED</scp>) study
Authors: Gerasimos Filippatos, Aldo P. Maggioni, Carolyn S.P. Lam, Elisabeth Pieske‐Kraigher, Javed Butler, John Spertus, Piotr Ponikowski, Sanjiv J. Shah, Scott D. Solomon, Andrea‐Viviana Scalise, Katharina Mueller, Lothar Roessig, Luke Bamber, Mihai Gheorghiade, Burkert Pieske
Journal: European Journal of Heart Failure (2017)