tbuckley/cabot-search huggingface dataset:
Survival of HIV-positive patients starting antiretroviral therapy between 1996 and 2013: a collaborative analysis of cohort studies
Authors: Adam Trickey, Margaret T May, Jorg-Janne Vehreschild, Niels Obel, M John Gill, Heidi M Crane, Christoph Boesecke, Sophie Patterson, Sophie Grabar, Charles Cazanave, Matthias Cavassini, Leah Shepherd, Antonella d'Arminio Monforte, Ard van Sighem, Mike Saag, Fiona Lampe, Vicky Hernando, Marta Montero, Robert Zangerle, Amy C Justice, Timothy Sterling, Suzanne M Ingle, Jonathan A C Sterne
Journal: The Lancet HIV (2017)

BackgroundHealth care for people living with HIV has improved substantially in the past two decades. Robust estimates of how these improvements have affected prognosis and life expectancy are of utmost importance to patients, clinicians, and health-care planners. We examined changes in 3 year survival and life expectancy of patients starting combination antiretroviral therapy (ART) between 1996 and 2013.MethodsWe analysed data from 18 European and North American HIV-1 cohorts. Patients (aged ≥16 years) were eligible for this analysis if they had started ART with three or more drugs between 1996 and 2010 and had at least 3 years of potential follow-up. We estimated adjusted (for age, sex, AIDS, risk group, CD4 cell count, and HIV-1 RNA at start of ART) all-cause and cause-specific mortality hazard ratios (HRs) for the first year after ART initiation and the second and third years after ART initiation in four calendar periods (1996–99, 2000–03 [comparator], 2004–07, 2008–10). We estimated life expectancy by calendar period of initiation of ART.Findings88 504 patients were included in our analyses, of whom 2106 died during the first year of ART and 2302 died during the second or third year of ART. Patients starting ART in 2008–10 had lower all-cause mortality in the first year after ART initiation than did patients starting ART in 2000–03 (adjusted HR 0·71, 95% CI 0·61–0·83). All-cause mortality in the second and third years after initiation of ART was also lower in patients who started ART in 2008–10 than in those who started in 2000–03 (0·57, 0·49–0·67); this decrease was not fully explained by viral load and CD4 cell count at 1 year. Rates of non-AIDS deaths were lower in patients who started ART in 2008–10 (vs 2000–03) in the first year (0·48, 0·34–0·67) and second and third years (0·29, 0·21–0·40) after initiation of ART. Between 1996 and 2010, life expectancy in 20-year-old patients starting ART increased by about 9 years in women and 10 years in men.InterpretationEven in the late ART era, survival during the first 3 years of ART continues to improve, which probably reflects transition to less toxic antiretroviral drugs, improved adherence, prophylactic measures, and management of comorbidity. Prognostic models and life expectancy estimates should be updated to account for these improvements.FundingUK Medical Research Council, UK Department for International Development, EU EDCTP2 programme.
Real-world treatment patterns in U.S. mRCC patients who fail two lines of targeted therapy.
Authors: Elisabetta Malangone, Magdaliz Gorritz, Lee Stern, John H. Coombs, James D. Turnbull, Zhimei Liu, Sumanta Kumar Pal
Journal: Journal of Clinical Oncology (2013)

e15511 Background: The treatment landscape for mRCC has undergone rapid growth in recent years with the approval of several targeted therapies (TTs). An analysis of real-world treatment patterns in patients who fail two lines of TT using the MarketScan database was recently presented (Pal S et al ASCO GU 2013 [Abstr 231]). The current study aimed to assess treatment patterns in mRCC patients who fail 2nd line TT using the PharMetrics database. Methods: Data were obtained from the PharMetrics database for patients with an RCC diagnosis and at least 3 lines of TT between January 1, 2004 and September 30, 2011. The PharMetrics database covers over 100 health plans across the U.S, and is plan-based, unlike MarketScan which is employer-based. Adult patients with at least 3 months of follow-up prior to initiation of 3rd line TT were included. Treatment patterns were examined for the final sample. Time to treatment discontinuation (TTD) was defined as the time from initiation of 1st line to end of 3rd line TT. Patients who did not switch to a 4th line TT were censored at end of 3rd line. Results: 377 mRCC patients initiated 3rd line therapy with sorafenib (So), sunitinib (Su), bevacizumab (Be), temsirolimus (Te), everolimus (Ev), or pazopanib (Pa). The sample was majority male (71%) with a mean age of 61 years (SD=10.5). The most common metastatic sites at any time were lung (76%) and bone (56%). The most common 1 st line agent was Su (46%) and the most common 2 nd line single agents were Te (26%) and Ev (17%). The most frequently used single agents in 3 rd line were Te (23%), Be (17%) and Ev (15%). Third-line treatment choice differed by year; Te (49%) was most common in 2007 while Ev and Pa were most common between 2010 and 2011. The most common sequences were VEGF-&gt;mTOR-&gt;VEGF (41%), VEGF-&gt;VEGF-&gt;mTOR (22%), and VEGF-&gt;mTOR-&gt;mTOR (11%). The median TTD in months, adjusted for censoring were as follows (median (25 th -75 th percentile): VEGF-&gt;mTOR-&gt;VEGF: 36.9 (23.3-NA); VEGF-&gt;VEGF-&gt;mTOR: 27.7 (15.74-NA); VEGF-&gt;mTOR-&gt;mTOR: 29.9 (18.3-38.0). Conclusions: These results confirm those presented at ASCO GU. There is a growing number of TTs being prescribed in 3 rd line mRCC patients. TTD results suggest an average treatment period of 32 months for the overall study sample.
Abstract IA09: Non-mutational resistance to anti-cancer drugs
Authors: Jeff Settleman
Journal: Clinical Cancer Research (2017)

Abstract “Rationally-targeted” oncology drugs can deliver significant therapeutic benefit in genomically-defined subsets of cancer patients. However, the clinical benefit associated with these agents is substantially limited by the nearly invariable emergence of drug resistance over time. In many cases, specific mutational mechanisms of resistance have been elucidated, presumably reflecting the clonal selection of stochastically-generated mutations that were present prior to treatment; however, additional pre-clinical and clinical findings implicate non-mutational mechanisms as well. We have identified and characterized a small subpopulation of reversibly “drug-tolerant” cells. The drug-tolerant phenotype is associated with a distinct chromatin state, and is transiently acquired and relinquished at low frequency by individual cells within the population, implicating the dynamic regulation of phenotypic heterogeneity. The drug-tolerant subpopulation can be selectively ablated by treatment with certain chromatin-modifying agents, potentially yielding a therapeutic opportunity. Furthermore, this subpopulation appears to contain the precursors of drug-resistant clones that acquire mutations during, rather than prior to, drug treatment. Additional studies of non-mutational drug resistance mechanisms implicate the rewiring of growth factor-responsive cellular signaling pathways as a common survival mechanism within tumor cell populations. These findings suggest that cancer cell populations employ various epigenetically-determined survival strategies to establish sufficient phenotypic variation among cells in order to protect the population from eradication by potentially lethal exposures. Citation Format: Jeff Settleman. Non-mutational resistance to anti-cancer drugs. [abstract]. In: Proceedings of the AACR Precision Medicine Series: Targeting the Vulnerabilities of Cancer; May 16-19, 2016; Miami, FL. Philadelphia (PA): AACR; Clin Cancer Res 2017;23(1_Suppl):Abstract nr IA09.
Spleen stiffness measurement: a useful prognostic tool in HCV patients treated with DAAs regimens
Authors: F. Ravaioli, G. Marasco, M.L.B. Reggiani, G. Mazzella, F. Buonfiglioli, A. Porro, S. Brillanti, A. Colecchia, D. Festi
Journal: Journal of Hepatology (2017)
Abstract 17870: Cardiac Computed Tomography Guides Ventricular Tachycardia Ablation
Authors: Kelvin C Chua, Ronald P Karlsberg, Eli S Gang
Journal: Circulation (2016)

Background:  Cardiac MRI characterizes scar tissue and identifies the heterogeneous zones (HZ) which may represent target vulnerable myocardium that guides ventricular tachycardia (VT) ablation strategies. Unfortunately, cardiac MRI is often contraindicated due to implantable devices. Cardiac computed tomography (CT) also characterizes tissues and has the advantage of being able to be used with implantable devices; however, its role for VT ablation is emerging and has only been defined with delayed enhancement which requires two acquisitions.   Methods:  We performed CT in 3 consecutive patients undergoing VT ablations. Non-delayed LV images were processed into 17-segment bulleyes and further partitioned into 2880 detailed sub-segments to generate Hounsfield units (HU) polar maps and colour-scale overlays to enhance subtle transitions of attenuation in order to define HZ (Vitrea®). During electrophysiology study (EPS), an endocardial bipolar voltage map of the LV was created using a 3D electroanatomical mapping system with a standard voltage criteria (scar  1.5mV in purple) and this was compared to the CT.   Results:  Single acquired CT accurately identified the HZ and correlated to the voltage map ascertained by the mapping system. Figures: A-VT morphology. B-Polar map with averaged-HU identifying basal inferior and inferolateral segments as HZ zone. C-CT image of the LV basal inferior aneurysm. D-Endocardial bipolar voltage map with excellent correlation to the CT. The critical isthmuses of VTs in all 3 patients determined during EPS localized to the same HZ identified on CT. Radiofrequency ablation successfully terminated the VT with acute non-inducibility.   Conclusion:  Cardiac CT with enhanced 2880 sub-segmental attenuation analysis defines HZ zones, cardiac anatomy, function, guides successful VT ablation with single acquisition, less radiation and has the potential to improve or have advantages to delayed enhancement techniques.
DARING-B: discontinuation of effective entecavir or tenofovir therapy in non-cirrhotic HBeAg-negative chronic hepatitis B patients: a prospective Greek study
Authors: G. Papatheodoridis, E. Rigopoulou, M. Papatheodoridi, K. Zachou, V. Xourafas, N. Gatselis, J. Vlachogiannakos, G. Dalekos
Journal: Journal of Hepatology (2017)
Approaches to fabricate practical recellularized liver graft using primary liver cells-our seeding method for optimal distribution of parenchymal and endothelial cells
Authors: H. Kojima, K. Yasuchika, K. Fukumitsu, T. Ishii, S. Ogiso, Y. Miyauchi, R. Yamaoka, T. Kawai, H. Katayama, E. Yoshitoshi, S. Kita, K. Yasuda, N. Sasaki, J. Komori, S. Uemoto
Journal: Journal of Hepatology (2017)
Measures of polypharmacy and chemotherapy toxicity in older adults with cancer.
Authors: Ronald John Maggiore, Tao Feng, William Dale, Cary Philip Gross, William P. Tew, Supriya Gupta Mohile, Cynthia Owusu, Heidi D. Klepin, Stuart M. Lichtman, Ajeet Gajra, June M McKoy, Vani Katheria, Rupal Ramani, Reena Jayani, Jaycen Brown, Arti Hurria
Journal: Journal of Clinical Oncology (2013)

9545 Background: Polypharmacy is common and associated with adverse clinical outcomes in older adults. Potentially inappropriate medication (PIM) use serves as an adjunctive assessment of polypharmacy. The goals of this study in an outpatient population of older adults with cancer (CA) were: 1) to estimate the prevalence of polypharmacy using multiple measures; and 2) to determine the relationship between polypharmacy and chemotherapy (chemo) toxicity. Methods: Medication use was evaluated in 500 patients (pts) age ≥65 years with invasive CA who were starting a new chemo regimen. Polypharmacy was defined by number of daily medications (meds), including non-prescription meds. PIM use was defined by 4 indices: Beers (2003 and 2012 update), Zhan, and HEDIS Drugs to Avoid in the Elderly (DAE) criteria. Prevalence of polypharmacy, PIM, and their association with grade 3-5 chemo toxicity [NCI Common Toxicity Criteria (v. 3.0)] were analyzed using chi square test and unconditional logistic regression. Results: All 500 pts were evaluable [mean age, 73 years (range 65-91); 56% female; 61% stage IV]. The mean number of daily meds was 5 (range 0-23); 38% used ≤3 daily meds, 51% used 4-9 meds, and 11% using ≥10 meds. Using 0-3 daily meds as the referent group, no association was found between daily meds and chemo tox: 4-9 meds, OR 1.34 (95% CI: 0.92-1.97); ≥10, OR 0.82 (95% CI: 0.45-1.49). PIM use was identified in 87 (17%), 147 (29%), 54 (11%), and 69 (13%) patients utilizing the 2003 Beers, 2012 Beers, Zhan, and HEDIS DAE criteria, respectively. There was no association between each PIM use index and chemo toxicity (p&gt;0.10 for all). Conclusions: Polypharmacy and PIM use were common in the geriatric oncology population. Although polypharmacy did not increase the risk of chemotherapy toxicity in this sample, further studies of polypharmacy’s impact on additional outcomes, including non-chemotherapy adverse drug events, in older persons with cancer are warranted.
Waiting times at their “worst,” but quality of care holds up
Authors: Anne Gulland
Journal: BMJ (2017)

Waiting times for many NHS urgent and emergency services in England were at their worst in five years in 2016-17, but there is no evidence yet that the care of patients has worsened, an analysis by the think tank the Health Foundation has found.1

In a second pre-election briefing the foundation analysed urgent and emergency services in the NHS, as well as quality of care, and found that it was too early to say whether the pressures on the NHS meant that quality was suffering.

The analysis of NHS England data shows that the target for treating 95% of patients within four hours of their arrival at a hospital emergency department was missed, with only 89.1% of patients being seen in 2016-17, meaning that 2.5 …
Changes in markers of liver function in hepatitis C virus genotype 1b Asian patients with compensated cirrhosis treated with ombitasvir/paritaprevir/ritonavir plus dasabuvir with ribavirin in the ONYX-II study
Authors: J. Heo, Y. Luo, W.-L. Chuang, J. Jia, K.-H. Han, M.-L. Yu, H. Tang, Y.-S. Lim, C.-Y. Peng, M. Xu, M. Wang, B. Fu, N. Mobashery, L. Wei
Journal: Journal of Hepatology (2017)
Increases in Biomarkers of Hyperglycemia With Age in the Atherosclerosis Risk in Communities (ARIC) Study
Authors: Bethany Warren, Andreea M. Rawlings, Alexandra K. Lee, Morgan Grams, Josef Coresh, Elizabeth Selvin
Journal: Diabetes Care (2017)

The American Diabetes Association’s Standards of Medical Care in Diabetes—2017 states that age should be “taken into consideration” when diagnosing diabetes with HbA1c (1). Nonetheless, it is unclear how this recommendation might be implemented. Population studies demonstrate that HbA1c increases with age, which some experts have suggested may be due to nonglycemic factors like alterations in red cell turnover or hemoglobin glycation (2–4). However, prior studies lack concurrent comparisons across nonhemoglobin-related markers of hyperglycemia. We evaluated increases with age in fructosamine and glycated albumin—hemoglobin-independent measures of hyperglycemia—in comparison with HbA1c and fasting glucose in the community-based Atherosclerosis Risk in Communities (ARIC) study.

We conducted serial cross-sectional analyses at visit 2 (1990–1992; n = 11,632) and visit 5 (2011–2013; n = 3,876), excluding individuals with diagnosed diabetes. We performed adjusted linear regression of z scores of each biomarker (standardized to visit 2) on age to allow head-to-head comparisons of the associations.

Age was significantly correlated with all biomarkers of hyperglycemia at visit 2 (Fig. 1). In middle …
Impact of survival after moving onto the end-of-life care in patients with hepatocellular carcinoma
Authors: S. Ogasawara, T. Wakamatsu, T. Chiba, M. Yokoyama, M. Inoue, T. Saito, E. Suzuki, Y. Ooka, A. Tawada, O. Yokosuka
Journal: Journal of Hepatology (2017)
Prognostic nomogram in elderly patients with glioblastoma.
Authors: Mital Patel, Neda Hashemi-Sadraei, Paul Elson, Manmeet Singh Ahluwalia
Journal: Journal of Clinical Oncology (2012)

2096 Background: Glioblastoma (GBM) is the most common malignant primary brain tumor. More than half the cases occur in patients aged ≥65 years; however, there is limited data on specific prognostic factors in these patients and there is a lack of easy to use nomograms in elderly GBM patients to provide them prognostic information. Methods: The Cleveland Clinic Brain Tumor and Neuro-Oncology Center’s database was used to identify elderly patients with GBM ( ≥65 years at the time of diagnosis). Multivariable analysis was conducted to identify independent predictors of survival using a Cox proportional hazards model and a stepwise selection algorithm with p=.10 as criteria for entry and retention. "Points" were assigned to each of these poor prognostic features and prognostic groups were formed based on the total number of calculated points. Results: 512 GBM patients with a median age of 73 years (range 65-96, 54% male) were included in the final analysis. On multivariable analysis six factors were identified as having an independent impact on overall survival after controlling for non-surgical treatment related factors like chemotherapy and radiation: age at diagnosis (p&lt;.0001), surgery (p&lt; .0001), multifocal disease (p=.0008), seizure at presentation (p=.02), hypertension (p=.05) and Karnofsky Performance Status (p&lt;.0001). Prognostic groups were developed as summarized in the table. 28% of the patients had the most favorable profile which was associated with 56% one year survival and a 13.2 months median survival. In contrast, almost all patients in the least favorable group (27%) died within one year. Conclusions: This is an easy to use nomogram in elderly GBM patients to provide them prognostic information. [Table: see text]
Fixed dose rate (FDR) gemcitabine as radiosensitizer for newly diagnosed glioblastoma multiforme (GBM): Preliminary results of a phase II study
Authors: A. Fabi, A. Felici, M. A. Mirri, G. Metro, A. Vidiri, A. Pace, M. A. Carosi, F. Cognetti, E. Occhipinti, C. M. Carapella
Journal: Journal of Clinical Oncology (2007)

12502 Background: In a previous phase I study (ASCO 2006), where FDR Gemcitabine at 10/mg/m 2 /min was tested in association with radiotherapy (RT) for the treatment of newly diagnosed GBM, a maximum tolerated dose of 175 mg/m 2 /wk was identified. Methods: After surgery for GBM (either citoreduction or sterebiopsy), patients were treated with fractionated focal RT at a daily dose of 2.0 Gy per fraction, five days per week for six weeks (total dose of 60 Gy). FDR Gemcitabine at 175 mg/m 2 /wk was given concomitantly starting 24–72 hours prior to RT and then for the whole duration of RT. An MRI performed at 7 and 40 days from the end of chemo-radiotherapy was used for activity assessment. Standard oral temozolamide 150–200 mg/m 2 was administrated following the combined treatment. Results: From 07/2004 16 patients (9 male, 7 female) have been enrolled. Characteristics of patients were: median age 57 years (42–72), median KPS at baseline 90 (70–100), surgery/stereobiopsy 14/2. Median time from diagnosis to initiation of Gemcitabine was 45 days (28–54). Among the 14 evaluable patients 3 (21.4%) partial responses, 7 (50%) stable disease and 4 (28.5%) progressive diseases were recorded. At a median follow up of 18 months (2–33) time to progression was 6 months (1.5–24). Toxicity was manageable with only one G3 neutropenia and hypertransaminasemia in two patients respectively. Grade 1 hypertransaminasemia was registered in 6 patients (43%). Conclusions: These preliminary results show that in patients with newly diagnosed GBM, radiosensitizing FDR Gemcitabine at 175 mg/m 2 /wk is a well tolerated regimen with an interesting activity. Accrual is ongoing and final results will be presented at the meeting. No significant financial relationships to disclose.
IVA337, a pan-ppar agonist, reduces non-alcoholic steatohepatitis feature and inhibits the inflammasome in murin models of non-alcoholic steatohepatitis
Authors: G. Wettstein, L. Poekes, F. Oakley, P. Faye, J.-M. Luccarini, P. Broqua, J.-L. Junien, D. Mann, I. Leclercq, I. Konstantinova
Journal: Journal of Hepatology (2017)
Implementation of Systemic Hedgehog Inhibitors in Daily Practice as Neoadjuvant Therapy
Authors: Nikki Tang, Desiree Ratner
Journal: Journal of the National Comprehensive Cancer Network (2017)

The most common cancer in both men and women is basal cell carcinoma (BCC). Although most primary and recurrent BCCs have high cure rates with standard therapies, advanced BCCs present a greater treatment challenge, especially in cosmetically and functionally sensitive areas. In patients unable to undergo surgery or radiation therapy, hedgehog inhibitors can be used neoadjuvantly to reduce tumor size, decreasing the extent and complexity of any subsequent surgery and providing either a cure or palliation. The goal of this review is to summarize the pharmacology, efficacy, and safety of systemic hedgehog inhibitors, as well as their role in daily practice as neoadjuvant therapy. Relevant English-language literature was identified and evaluated based on results from database searches of PubMed. Terms searched included, but were not limited to, "vismodegib," "Erivedge," "sonidegib," "DE225," "BCC," and "neoadjuvant treatment." Additional literature was identified from the reference lists of previously identified articles. The authors' personal experience in treating advanced BCC using hedgehog inhibitors has been incorporated into the recommendations made herein.
Abstract #3526: Benzyl isothiocyanate induces nuclear translocation of AhR and its heterodimerization with ARNT in Hepa1c1c7 cells
Authors: Stephen Kioko, Michael Powell, Ward Kirlin
Journal: Cancer Research (2009)

The biotransformation and detoxification of carcinogens, including 2,3,7,8-tetrachlorodibenzo dioxin, benzo [a] pyrene and 3-methylchloranthrene is dependent upon the activity of phase I and II enzymes, particularly CYP1A1 and NQO1. The transcriptional activation of these enzymes is regulated by the aryl hydrocarbon receptor (AhR) and Nuclear Factor-Erythroid 2-Related Factor. These transcription factors reside in the cytoplasm and when activated, shed their respective chaperones and translocate into the nucleus where they interact with nuclear proteins involved with transcription of genes possessing xenobiotic (XRE) and antioxidant (ARE) response elements. We have observed that the phytochemical benzyl isothiocyanate (BIT) induces nuclear translocation of the AhR independently of traditional ligands in Hepa1c1c7 cells suggesting that it might bind the AhR and affect activity of these enzymes as well as the expression of XRE-responsive genes. As a first step in addressing this hypothesis, we investigated whether BIT activates the AhR, causing it to form heterodimers with ARNT in the nuclei of Hepa1 cells. Cells were treated with 5, 10 and 20 µM BIT or DMSO alone. \#946;-Napthoflavone (BNF) was used as a positive control to visualize AhR/ARNT heterodimerization. Using in vitro-activation of Hepa-1 cell lysates as well as nuclear co-immunoprecipitation and mass spectrometry, we observed that AhR/ARNT heterodimerization occurred in the nucleus of Hepa1 cells treated with BIT similar to what was seen in response to BNF. Additionally, Western blot analysis verified that AhR interacted with ARNT in these cells. The results therefore suggest that BIT alone, a know inducer of Phase II enzyme expression, might activate the AhR and facilitate its binding to several genes that regulate cellular function, including genes associated with activation and detoxification of carcinogens. (Support: NIH MBRS/GM028248; RCMI RR033032)  Citation Information: In: Proc Am Assoc Cancer Res; 2009 Apr 18-22; Denver, CO. Philadelphia (PA): AACR; 2009. Abstract nr 3526.