tbuckley/cabot-search huggingface dataset:
Prognostic testing patterns in CLL pts treated in U.S. practices from the Connect CLL registry.
Authors: Anthony Mato, Christopher Flowers, Charles Michael Farber, Mark Adam Weiss, Thomas J. Kipps, Mark Kozloff, Chadi Nabhan, Ian Flinn, David L. Grinblatt, Nicole Lamanna, Kristen A. Sullivan, Pavel Kiselev, E. Dawn Flick, Kenneth A. Foon, Arlene S. Swern, Jeff Porter Sharman
Journal: Journal of Clinical Oncology (2015)

7013 Background: Genetic aberrations detected by fluorescence in situ hybridization (FISH) and cytogenetic (CG) testing provide prognostic information for CLL pts. The identification of genetic abnormalities has particular relevance in choosing immunochemo- or kinase inhibitor therapies, SCT or clinical trial. Here, we analyze factors influencing decisions to perform FISH or CG testing. Methods: Connect CLL is a large, prospective, longitudinal, multicenter, observational registry of 1494 CLL pts at 179 community (n=1,311), 17 academic (n=155), and 3 government (n=28) sites. Pts were enrolled within 2 months of initiating any line of therapy (LOT). Univariate (UV) and multivariate (MV) logistic regression analyses were conducted to identify characteristics associated with a decision to perform genetic testing at LOT1 and at LOT≥2. Results: FISH or CG was performed at study enrollment in 861/1,494 (58%) pts (36% CG, 49% FISH, 28% both). 65% of 889 pts were tested for FISH/CG prior to LOT1, 50% of 260 in LOT2, 45% of 345 in LOT>3. Of 861 pts tested at enrollment, 29% had FISH/CG retested with a subsequent LOT. In UV analyses (14 predictors), FISH/CG were more often performed at academic sites (p .005), in pts age ≤75 (p .0002), at enrollment at LOT1 vs. LOT ≥2 (p < .0001), in private insurance pts (p .002) and Rai stage ≥2 (p<.0001). Table 1 describes independent predictors of performing genetic testing stratified by LOT and practice setting. Conclusions: Our results indicate that only a fraction of CLL pts are tested/re-tested for genetic alterations by FISH/CG. Given the significance of identifying del17p or complex CG in selecting each LOT, these results indicate a need for increased awareness of the importance of this testing. MV analysis: Predictors of FISH/CG. Time point/Practice setting Covariate OR 95% CI LOT1/All sites Academic vs community-govt site 1.76 1.03-2.99 White vs other 1.90 1.13-3.17 Private insurance 1.44 1.08-1.92 LOT1/Community-Govt sites White vs other 2.40 1.26-4.58 Age≤75 vs. < 75 1.44 1.01-2.05 RAI stage ≥2 vs. 1 1.52 1.07-2.14 LOT≥2:/All sites White vs other 0.34 0.17-0.68 Age≤75 1.45 1.01-2.07 LOT≥2/Community-Govt sites White vs other 0.41 0.16-1.04 Age≤75 1.65 1.05-2.61 RAI stage ≥2 1.74 1.12-2.71
Why Michael Couldn't Hit and Other Tales of Neurology of Sports
Authors: Kim Hutton
Journal: BMJ (1999)

Harold Klawans is an author so good I'll buy his books in hardback. Why Michael Couldn't Hit is a book to keep and reread again and again. In the same format as the earlier Toscanini's Fumble and Newton's Madness , here are neurological anecdotes about individuals, in this case sportspeople. But the reader does not need to …
The cell in the ink: Improving biofabrication by printing stem cells for skeletal regenerative medicine
Authors: G. Cidonio, M. Glinka, J.I. Dawson, R.O.C. Oreffo
Journal: Biomaterials (2019)

Recent advances in regenerative medicine have confirmed the potential to manufacture viable and effective tissue engineering 3D constructs comprising living cells for tissue repair and augmentation. Cell printing has shown promising potential in cell patterning in a number of studies enabling stem cells to be precisely deposited as a blueprint for tissue regeneration guidance. Such manufacturing techniques, however, face a number of challenges including; (i) post-printing cell damage, (ii) proliferation impairment and, (iii) poor or excessive final cell density deposition. The use of hydrogels offers one approach to address these issues given the ability to tune these biomaterials and subsequent application as vectors capable of delivering cell populations and as extrusion pastes. While stem cell-laden hydrogel 3D constructs have been widely established in vitro, clinical relevance, evidenced by in vivo long-term efficacy and clinical application, remains to be demonstrated. This review explores the central features of cell printing, cell-hydrogel properties and cell-biomaterial interactions together with the current advances and challenges in stem cell printing. A key focus is the translational hurdles to clinical application and how in vivo research can reshape and inform cell printing applications for an ageing population.
Triple therapy for all patients with severe symptomatic COPD at risk of exacerbations
Authors: Alberto Papi, Stefano Petruzzelli, Stefano Vezzoli, George Georges, Leonardo M. Fabbri
Journal: European Respiratory Journal (2019)

<b>In keeping with the latest international recommendations, we suggest using triple therapy in all patients with severe symptomatic COPD at increased risk of exacerbation who are not adequately treated by LAMA/LABA or LABA/ICS, independent of asthma history</b>http://ow.ly/Bbsr30nXffO
Genomic profiling of patients with multiple primary cancers reveals different cancer gene mutation pathways.
Authors: Yan Ding, Ruoyu Wang
Journal: Journal of Clinical Oncology (2015)

e22050 Background: Multiple primary cancers in a single individual are rare and usually challenging for effective treatments. Identification common cancer gene driver mutations and targets for patients with multiple primary malignant cancers will offer potential opportunities for effective personalized treatment. Methods: We have collected and analyzed tumor tissue samples from patients diagnosed with multiple primary cancers including lung cancer, kidney caner, prostate cancer, and bone caner from the Affiliated Zhongshan Hospital of Dalian University. Deep sequencing of the tumor samples was done using TruSeq Amplicon - Cancer Panel (TSACP) which covers 48 cancer genes with more than 400 mutation hotspots. Results: We have found that TP53 (75%), PIK3CA (50%), KDR(50%), VHL(50%), KRAS (25%), , FGFR(30%), EGFR(25%), HER2(25%) and ATM (25%) mutations are among the most common gene alterations across different types of primary cancers, they share some common cancer gene pathways. Missense exon variation(4.13%) , non-coding exone variation(2.8%), and frameshift variation (0.41%) are among the most frequent alterations for functional effects. Personalized treatments according to the individual cancer gene mutation profiles have been recommended. Conclusions: Cancer hot-spot gene mutations in patients with multiple primary cancers have been investigated using next generation sequencing technologies. Common driver mutations and pathways among the different cancers have been identified, and targeted and chemotherapies have been suggested for personalized cancer treatments.
External Validation of a Pretransplant Biomarker Model (REVERSE) Predictive of Renal Recovery After Liver Transplantation
Authors: Josh Levitsky, Sumeet K. Asrani, Michael Abecassis, Richard Ruiz, Linda W. Jennings, Goran Klintmalm
Journal: Hepatology (2019)

In patients with end‐stage liver disease, the ability to predict recovery of renal function following liver transplantation (LT) remains elusive. However, several important clinical decisions depend on whether renal dysfunction is recoverable after LT. We used a cohort of patients undergoing LT to independently validate a published pre‐LT model predictive of post‐transplant renal recovery (Renal Recovery Assessment at Liver Transplant [REVERSE]: high osteopontin [OPN] and tissue inhibitor of metalloproteinases‐1 [TIMP‐1] levels, age &lt; 57, no diabetes). Serum samples pre‐LT and 4‐12 weeks post‐LT (n = 117) were analyzed for kidney injury proteins from three groups of recipients: (1) estimated glomerular filtration rate (eGFR) &lt; 30 mL/minute/1.73 m 2 prior to and after LT (irreversible acute kidney injury [AKI]), (2) eGFR &lt; 30 mL/minute/1.73 m 2 prior to LT and &gt;50 mL/minute/1.73 m 2 after LT (reversible AKI [rAKI]) (3) eGFR &gt; 50 mL/minute/1.73 m 2 prior to and after LT (no AKI). In patients with elevated pre‐LT serum levels of OPN and TIMP‐1, recovery of renal function correlated with decreases in the level of both proteins. At 4 weeks post‐LT (n = 77 subset), the largest decline in OPN and TIMP‐1 was seen in the rAKI group. Validation of the REVERSE model in this independent data set had high area under the curve (0.78) in predicting full post‐LT renal recovery (sensitivity 0.86, specificity 0.6, positive predictive value 0.81, negative predictive value 0.69). Our eGFR findings were confirmed using measured GFR. Conclusion : The REVERSE model, derived from an initial training set combining plasma biomarkers and clinical characteristics, demonstrated excellent external validation performance characteristics in an independent patient cohort using serum samples. Among patients with kidney injury pre‐LT, the predictive ability of this model may prove beneficial in clinical decision‐making both prior to and following transplantation.
Exploiting DNA Replication Stress for Cancer Treatment
Authors: Tajinder Ubhi, Grant W. Brown
Journal: Cancer Research (2019)

Complete and accurate DNA replication is fundamental to cellular proliferation and genome stability. Obstacles that delay, prevent, or terminate DNA replication cause the phenomena termed DNA replication stress. Cancer cells exhibit chronic replication stress due to the loss of proteins that protect or repair stressed replication forks and due to the continuous proliferative signaling, providing an exploitable therapeutic vulnerability in tumors. Here, we outline current and pending therapeutic approaches leveraging tumor-specific replication stress as a target, in addition to the challenges associated with such therapies. We discuss how replication stress modulates the cell-intrinsic innate immune response and highlight the integration of replication stress with immunotherapies. Together, exploiting replication stress for cancer treatment seems to be a promising strategy as it provides a selective means of eliminating tumors, and with continuous advances in our knowledge of the replication stress response and lessons learned from current therapies in use, we are moving toward honing the potential of targeting replication stress in the clinic.
Nontuberculous mycobacterial pulmonary disease and <i>Aspergillus</i> co-infection: Bonnie and Clyde?
Authors: Kim Geurts, Sanne M.H. Zweijpfenning, Lian J. Pennings, Jodie A. Schildkraut, Martin J. Boeree, Cecile Magis-Escurra, Henrich van der Lee, Paul E. Verweij, Wouter Hoefsloot, Jakko van Ingen
Journal: European Respiratory Journal (2019)

<b>40% of patients diagnosed with nontuberculous mycobacterial lung disease also meet diagnostic criteria for chronic pulmonary aspergillosis and <i>Mycobacterium avium</i> stimulates <i>Aspergillus</i> growth <i>in vitro</i></b>http://bit.ly/2JmLKk5
Abstract MP093: Preterm Delivery is Associated with Maternal Cardiovascular Risk Factors
Authors: Lauren J Tanz, Jennifer J Stuart, Eric B Rimm, Paige L Williams, Stacey A Missmer, Janet W Rich-Edwards
Journal: Circulation (2017)

Background: Women with a history of delivering a child preterm have a higher risk of cardiovascular disease (CVD). We sought to evaluate whether these women are also at higher risk of developing CVD risk factors after adjustment for multiple pre-pregnancy risk factors. Methods: We examined the association between preterm delivery (&lt;37 weeks) and development of subsequent chronic hypertension, hypercholesterolemia, and type 2 diabetes mellitus (T2DM) among 59,315 women in the Nurses’ Health Study II. We restricted our study population to parous women who did not experience gestational diabetes or a hypertensive disorder in their first pregnancy and were free of CVD risk factors of interest and events at baseline. Multivariable Cox proportional hazards models were used to estimate hazard ratios (HRs) and 95% confidence intervals (CIs) for the associations between preterm delivery in first pregnancy and each CVD risk factor. We additionally investigated the association between preterm delivery over a woman’s entire reproductive history and CVD risk factors. Results: Compared to women who delivered their first pregnancy at term, preterm delivery was associated with HRs of 1.13 (95% CI: 1.07, 1.19) for chronic hypertension, 1.06 (95% CI: 1.02, 1.11) for hypercholesterolemia, and 1.21 (95% CI 1.08, 1.35) for T2DM, after adjusting for age, race/ethnicity, parental education, and other pre-pregnancy risk factors (e.g., BMI, smoking, family history of chronic hypertension and T2DM). These associations were stronger in the very preterm group (&lt;32 weeks) than in the moderate preterm group (≥32 to &lt;37 weeks). The risk was highest in the first 10 years after a preterm first birth with HRs of 1.45 (95% CI: 1.23, 1.71) for chronic hypertension, 1.13 (95% CI: 1.02, 1.25) for hypercholesterolemia, and 2.14 (95% CI: 1.33, 3.45) for T2DM. When investigating a woman’s entire reproductive history, we found that, compared to women with at least two births all of which were at term, women with a preterm first birth were at increased risk of chronic hypertension regardless of the gestation lengths of future pregnancies, while women with a preterm first birth and no future births had the highest risk of T2DM. Conclusions: Women with a history of preterm delivery have higher risk of developing chronic hypertension, hypercholesterolemia, and T2DM after pregnancy. These results suggest potential benefits of including preterm delivery in CVD risk scores and screening.
FRI-293-Recipient PNPLA3 and TM6SF2 genotypes and risk of NAFLD folllowing liver transplantation
Authors: Carmen Ester, Razvan Cerban, Speranta Iacob, Razvan Iacob, Georgiana Constantin, Prof. Dr. Liliana Pislaru, Dr. Sorop Andrei, Dr. Mihaela Ghioca, Dr. Lorand Savu, Prof. Dr. Irinel Popescu, Prof. Dr. Liana Gheorghe
Journal: Journal of Hepatology (2019)
HBV reactivation, flare and fulminant hepatitis in patients receiving non-rituximab chemotherapy.
Authors: Shin Ogita
Journal: Journal of Clinical Oncology (2015)

e20729 Background: Hepatitis B reactivation and fulminant hepatitis have been observed in patients (pts) who receive certain anti-neoplastic agents, specially rituximab. Such risks caused by other chemotherapeutic drugs are less known. Methods: Pts with positive HBs-antigen and/or detectable HBV-DNA who received chemotherapies were retrospectively identified. Serum AST, ALT, bilirubin, PT- INR and HBV-DNA were obtained from 3 months prior to the initiation of chemotherapy to one year after the last dose of chemotherapy. Flare and severe flare were defined as increase in ALT to > 5 times and > 10 times the upper limit of normal, respectively. HBV reactivation was defined as a > 10-fold increase in HBV-DNA. Fulminant hepatitis was defined as the development of encephalopathy and increase in INR to > 1.5 in addition to severe flare. Results: 119 pts with HBs-ag(+) and/ or HBV-DNA (+) received chemotherapy from July, 2003 to October, 2014 at St. Luke's International Hospital, Tokyo. Ten pts who received concurrent rituximab were excluded, and 109 pts were analyzed. 22 pts (20%), 63pts (58%), 34 pts (31%) and 75 pts (69%) received platinum , anthracycline, taxane and/or other chemotherapies, respectively. 25 pts (23%) developed flare and 10 of 25 were severe flare. Pre-chemotherapy HBV-DNA was tested in 25 pts, and one (4%) developed HBV reactivation without flare. Age, rate of antiviral therapy use, baseline ALT or HBV-DNA were not significantly different between those who developed flare and those who did not. Median duration of chemotherapy was significantly longer in pts who developed flare than those who did not. (6.2 months vs 4.2months, p = 0.04). Pts with hematological malignancies had highest risk of developing flare (67%) whereas risk of flare in breast, lung and other GI malignancy pts were low (8%, 9%, 12%, respectively). No pts developed fulminant hepatitis. Conclusions: Longer and more intensive chemotherapies may be associated with hepatic flare. Larger prospective studies are needed to further investigate the risk of HBV reactivation and fulminant hepatitis caused by commonly used chemotherapeutic drugs.
THU-487-Circulating MIR-4492 as a biomarker to predict therapy response and disease free survival in hepatocellular carcinoma
Authors: Muhammad Yogi Pratama, Alessia Visintin, Matteo Rossano Buonocore, Lory Saveria Crocè, Claudio Tiribelli, Devis Pascut
Journal: Journal of Hepatology (2019)
Heterogeneity score in inoperable stage III non-small cell lung cancer patients treated with definitive chemoradiotherapy: A single centre analysis
Authors: J. Taugner, L. Käsmann, C. Eze, M. Dantes, O. Roengvoraphoj, K. Gennen, M. Karin, A. Tufman, C. Belka, F. Manapov
Journal: Annals of Oncology (2019)

Background: Inoperable stage-III non-small cell lung cancer (NSCLC) represents a very heterogeneous disease in terms of patient and tumor characteristics. A simple heterogeneity score may help to personlize multimodal therapy. Methods: The data of 99 patients with performance status ECOG 0-1 treated with chemoradiotherapy (CRT) for inoperable stage III NSCLC, treated between 2011 and 2016 at our hospital were analyzed. Patient- and tumor-related factors were evaluated, and factors showing a significant negative association with patient survival were scored with one point each. Three subgroups with a low, intermediate and high-risk (0-1, 2-3 and 4-5 points) score were defined. The results were validated in a prospective cohort of 35 patients. Results: Concurrent CRT was administered in 78% (n = 78) of patients and sequential CRT in 11% (n = 11), 10 Patients were treated with radiotherapy alone. 53% (n = 53) of patients received induction chemotherapy. Median overall survival (mOS) for the entire cohort was 20.8 months. Age (p = 0.020), gender (p = 0.007), cumulative tobacco pack years (PY) (p = 0.015), tumor-associated atelectasis (p = 0.004) and histology (p = 0.011) had a significant impact on survival in univariate analysis. 12, 59 and 28 patients had low, intermediate and high-risk score. MS, 1-, 2- and 3-year survival rates were as follows: not reached, 100%, 83% and 67% in the low, 22.9 months, 80%, 47% and 24% in the intermediate and 13.7 months, 57%, 25% and 18% in the high-risk score subgroup. Prospective validation of the score demonstrated one-year survival of 100% for patients in the low-risk subgroup, 93% in the intermediate-risk subgroup, and 69% in the high-risk subgroup (p = 0.100). Conclusions: This simple heterogeneity score was developed for inoperable stage III NSCLC patients with good performance status receiving multimodal therapy. The score may aid physicians to infer clinical outcomes and optimize decisions concerning treatment strategies, as well as planning of prospective studies. Legal entity responsible for the study: The authors. Funding: Has not received any funding. Disclosure: All authors have declared no conflicts of interest.
TCTAP C-076 In-stent Restenosis with Chronic Total Occlusion at the Orifice of Left Circumflex Artery
Authors: Tien-Chi Huang, Chun-Yuan Chu, Wen-Hsien Lee, Po-Chao Hsu, Hung-Hao Lee, Cheng-An Chiu, Ho-Ming Su, Tsung-Hsien Lin, Chee-Siong Lee, Hsueh-Wei Yen, Wen-Chol Voon, Wen-Ter Lai
Journal: Journal of the American College of Cardiology (2019)
Correlation between hormones and growth factors in blood of rats with liver metastases.
Authors: Irina V. Kaplieva, Oleg Ivanovich Kit, Elena Mikhaylovna Frantsiyants, Lidia K. Trepitaki, Natalia D. Cheryarina, Irina Igorevna Gorina, Mikhail Anatolievich Kozhushko
Journal: Journal of Clinical Oncology (2015)

e22002 Background: Understanding of processes underlying the transformation of a normal cell into a tumor one is essential for the search for new methods of anticancer therapy. It is important to know the correlations between various components of the body systems and tumor. The purpose of this study was to investigate correlation between hormones and some growth factors in blood serum in liver metastasis. Methods: The study included 30 male rats (Wistаr) with liver metastases. Correlation between some hormones and growth factors in blood serum in development of liver metastasis was analyzed. Levels of adrenocorticotropic hormone (ACTH), follicle-stimulating hormone (FSG), thyroid-stimulating hormone (TSH), luteinizing hormone (LH), prolactin (PRL), progesterone (PRG), total testosterone (Test), corticosterone (Crt), free T4 (FT4) and free T3 (FT3) were detected with radioimmunoassay using standard reagents and levels of estrone, estradiol, dehydroepiandrosterone (DHEA), IGF-I, IGF-II and ТGF-β1– with ELISA using standard reagents. Results: Total amount of strong correlations between IGF-I, IGF-II and ТGF-β1 and the hormones decreased by 2 times during liver metastasis in comparison with primary tumor growth. IGF-I had 7 strong correlations, positive – with ACTH (0.91), DHEA (0.80), estradiol (0.96), PRL (0.95), TSH (0.91) and FT4 (0.76); negative – with estrone (-0.90). The other growth factors both had 2 strong correlations: IGF-II – positive ones with Crt (0.88) and FSH (0.90), ТGF-β1 – negative ones with Crt (-0.79) and Test (-0.92). Correlations of ТGF-β1were mainly negative mild ones, that of IGF-II – weak. Conclusions: Liver metastasis is accompanied by development of a more complex imbalanced system of hormonal influences on tumor growth which shows modification of hormonal regulation of metastasis combined with expression of IGF-I and ТGF-β1 in liver.
FRI-197-Prediction of elastographic reversion of cirrhosis after 5 years of entecavir or tenofovir disoproxil fumarate therapy in caucasian chronic hepatitis B patients
Authors: George Papatheodoridis, George Dalekos, Cihan Yurdaydin, Vana Sypsa, Florian van Bommel, Maria Buti, José Luis Calleja Panero, Heng Chi, Ioannis Goulis, Spilios Manolakopoulos, Alessandro Loglio, Theodoros Voulgaris, Nikolaos Gatselis, Onur Keskin, Rhea Veelken, Marta Lopez-Gomez, Bettina Hansen, savvoula savvidou, Anastasia Kourikou, Ioannis Vlachogiannakos, kostas galanis, Ramazan Idilman, Rafael Esteban, Harry Janssen, Thomas Berg, Pietro Lampertico
Journal: Journal of Hepatology (2019)