tbuckley/cabot-search huggingface dataset:
Blood pressure self screening in GP surgeries is acceptable to patients, study finds
Authors: Ingrid Torjesen
Journal: BMJ (2017)

Making more blood pressure (BP) monitors available to patients in GP waiting rooms could increase detection of high BP and help patients being treated for high BP to monitor and control it better, research published in the British Journal of General Practice suggests.1

Researchers from the University of Oxford conducted interviews with patients who attended GP surgeries where BP monitors were available for patients’ self use, either in the waiting room or another public area of the building, to find out why patients did or did not choose to use them.

A total of 30 patients were interviewed, of whom six (20%) were hypertensive and just under half (47%) had used a BP self screening …
Induction of Immune Reaction in Benign Melanocytic Nevi Without Halo During Nivolumab Therapy in a Patient With Melanoma
Authors: Yasuhiro Nakamura, Takashi Fujino, Hiroshi Kagamu, Taisuke Matsuya, Yukiko Teramoto, Yuri Asami, Akifumi Yamamoto
Journal: JAMA Dermatology (2017)

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Occurrence and recurrence of malignancies post DAA Treatment in 5.1% of patients- single center experience
Authors: A. Issachar, O. Sneh-Arbib, M. Braun, A. Shlomai, E. Oxtrud, Y. Harif, C. Karavani, R. Tur- Kaspa, M. Cohen-Naftaly
Journal: Journal of Hepatology (2017)
Impact of amino acid substitutions of HCV core region on hepatocarcinogenesis and hepatocellular oxidative stress in HCV infection
Authors: T. Chida, S. Watanabe, K. Kawata, M. Umemura, E. Matsunaga, J. Itoh, K. Ohta, S. Shimoyama, S. Yamazaki, T. Suzuki, Y. Kobayashi
Journal: Journal of Hepatology (2017)
NHS in danger of falling behind with out of date scanners, warn experts
Authors: Adrian O’Dowd
Journal: BMJ (2017)

Patient care could be held back by ageing scanners used in the NHS, warn imaging experts.

A report1 published by an intercollegiate expert advisory body called the Clinical Imaging Board (CIB) has said that more must be done to future proof the NHS’s capacity to use magnetic resonance imaging (MRI) to scan patients.

The board—a collaboration between the Royal College of Radiologists, the Society and College of Radiographers, and the Institute of Physics and Engineering in Medicine—carried out a survey of UK radiology teams to measure the state of MRI equipment.

It had responses from 73 organisations in relation to 171 MRI systems—representing 42% …
Dynamic of liver stiffness values by means of transient elastography in patients with hepatitis C virus liver cirrhosis undergoing Interferon free treatment
Authors: I. Sporea, R. Lupusoru, R. Mare, A. Popescu, R. Sirli, M. Danila, A. Lazar, S. Iacob, L. Sandulescu, L. Gheorghe
Journal: Journal of Hepatology (2017)
Abstract 375: Mechanotransduction via Titin’s N2B Element Contributes to Cardiac Remodeling
Authors: Mathew Bull, Pooja Nair, Joshua Strom, Michael Gotthardt, Henk Granzier
Journal: Circulation Research (2015)

Pathological remodeling is responsible for the functional deficits characteristic of heart failure patients. Understanding mechanotransduction is limited, but holds potential to provide novel therapeutic targets to treat patients with heart failure, especially those with diastolic dysfunction and preserved ejection fraction (HFpEF). Titin is the largest known protein and is abundant in muscle. It is the main contributor of passive stiffness in the heart and functions as a molecular mechano-sensor for stress and strain in the myocyte. Titin is composed of four distinct regions, (N-terminal Z-line, I-band, A-band, and C-terminal M-line), and acts as a molecular spring that is responsible for the assembly and maintenance of ultrastructure in the sarcomere. The elastic N2B element found in titin’s I-band region has been proposed as a mechano-sensor and signaling “hot spot” in the sarcomere. This study investigates the role of titin’s cardiac specific N2B element as sensor for stress and strain induced remodeling in the heart. The previously published N2B knock out (KO) mouse was subjected to a variety of stressors including transverse aortic constriction (TAC), aorto-caval fistula (ACF), chronic swimming, voluntary running and isoproterenol injections. Through chronic pathologic stress, pressure overload (TAC) and chronic volume overload (ACF), we found that the N2B element is necessary for the response to volume overload but not pressure overload as determined by changes in cardiac remodeling. Furthermore, the response to exercise either by chronic swimming or voluntary running was reduced in the N2B KO mouse. Finally, unlike the wild-type (WT) mouse, the N2B KO mouse did not respond to isoproterenol injections with hypertrophic remodeling. Ongoing work to elucidate the molecular pathways involving the N2B element and response to stress, is focused on its binding protein Four-and-a-half-LIM domains 2 (FHL2) and the mitogen activated protein kinase (MAPK) pathway. Taken together our data suggest that the N2B element contributes significantly to mechanotransduction in the heart.
Interest in Initiating Corticosteroids By Intravenous Methylprednisolone at Standard Dose in Newly Diagnosed Immune Thrombocytopenia Adults: Results of the Prospective Carmen Registry
Authors: Anaïs Essilini, Thibault Comont, Johanne Germain, Natacha Brun, Claire Dingremont, Brice Castel, Philippe Montané de la Roque, Serge Madaule, Laurent Sailler, Laurent Prudhomme, Sophie Arista, Laurent Balardy, Francis Gaches, Benjamin Hebraud, Cecile Borel, Stéphane Sire, Miguel Carreiro, Guillaume Martin-Blondel, Laurent Alric, Patrick Giraud, Maryse Lapeyre-Mestre, Odile Beyne-Rauzy, Daniel Adoue, Guillaume Moulis
Journal: Blood (2016)
Overall survival (OS) in patients with EGFR-mutated new diagnosed stage IIIB/IV NSCLC in addiction of exon 19, 18/20 and 21 mutation and in addiction of treatment with tyrosine kinase inhibitor (TKI) or chemotherapy: A subgroup analysis of the REASON trial.
Authors: Wolfgang Schuette, Timo Behlendorf, Peter Schirmacher, Wilfried Eberhardt, Manfred Dietel, Ute Zirrgiebel, Lars Muehlenhoff, Michael Thomas
Journal: Journal of Clinical Oncology (2015)

e19001 Background: Somatic mutations in the EGFR kinase domain strongly correlate with increased response to EGFR TKIs in NSCLC, yet limited information exists about EGFR mutations of all 4 exons in NSCLC. Methods: In an epidemiologic approach, the EGFR-mutation status of 4200 pts with newly diagnosed NSCLC was evaluated; 431 pts with mutation were detected. The initial therapy was not predefined by protocol. In a retrospective subgroup analysis in addiction to all mutations of exon 19, exon 21 or exon 18/20 the median OS in relation to the therapy with TKI or CTx was investigated. Results: Subgroup A TKI first-line: 121 of 156 pts with exon 19-mutation were treated with TKI, the other 35 pts received CTx. The median OS was 21.3 (95% CI 18.1 – NA) vs. 16.5 months (95% CI 12.1 – NA) [p = 0.1247]. In 47 pts with exon 18- or 20-mutation, the median survival was amounted for 24 pts with initial TKI treatment 21.3 months (95% CI 18.4 – NA) vs. 15.4 months (95% CI 6.9 – NA) for 23 pts without initial TKI therapy [p = 0.1737]. For 109 pts with exon 21-mutation, a difference between median OS of 14.1 months (95% CI 12.4 – 16.8) of 87 pts with TKI treatment vs. 14.2 months (95% CI 13.6 – NA) of 22 pts without TKI treatment could not be detected. Subgroup B TKI ever: Pts showed for exon 19-mutation a very clear survival benefit of 23.2 months (95% CI 18.4 – NA) for 129 pts with TKI treatment vs. 10.6 months (95% CI 4.6 – NA) for 22 pts who never received TKI [p = 0.0006]. The same was true for exon 18- or 20 mutation with 21.3 months (95% CI 18 – NA) for 26 pts treated with TKI vs. 8.3 months (95% CI 4.2 – NA) for 20 pts without TKI [p = 0.1621]. In contrast, for exon 21-mutation a median survival for 91 pts with TKI of 14.2 months (95% CI 12.6 – 18) and for 19 pts without TKI of 13.9 months (95% CI 10.5 – NA) was assessed. Conclusions: The therapy with TKI showed OS benefit for pts with exon 19-mutations. Also for exon 18- or 20-mutations, an advantage was evaluated whereas for exon 21-mutations, no difference between the OS data was observed regarding the therapy with TKI or CTx. The magnitude of benefit of TKI treatment may depend on the type of exon-mutations. Clinical trial information: NCT00997230.
Phase II Study of Everolimus in Patients With Thymoma and Thymic Carcinoma Previously Treated With Cisplatin-Based Chemotherapy
Authors: Paolo Andrea Zucali, Tommaso De Pas, Giovannella Palmieri, Adolfo Favaretto, Antonio Chella, Marcello Tiseo, Michele Caruso, Matteo Simonelli, Matteo Perrino, Fabio De Vincenzo, Francesca Toffalorio, Vincenzo Damiano, Giulia Pasello, Erika Garbella, Marco Ali, Fabio Conforti, Margaret Ottaviano, Angela Cioffi, Sabino De Placido, Laura Giordano, Monica Bertossi, Annarita Destro, Luca Di Tommaso, Armando Santoro
Journal: Journal of Clinical Oncology (2017)

Purpose No effective salvage treatments are available for patients with advanced/recurrent thymoma (T) or thymic carcinoma (TC) who have progressed after platinum-based chemotherapy. This study evaluated the activity of everolimus in patients with advanced/recurrent T or TC previously treated with cisplatin-containing chemotherapy. Patients and Methods This was a single-arm, single-stage, open-label, multicenter, phase II trial. Patients received oral everolimus 10 mg/d until disease progression, unacceptable toxicity, or patient refusal. A Fleming phase II trial was designed. The null hypothesis of a true disease control rate (DCR) of 40% was tested against a one-sided alternative of a true DCR of 60% (α = β = 0.10): If disease control were achieved in ≥ 21 of the first 41 evaluable patients, everolimus could be recommended for further evaluation. Progression-free survival, overall survival, and safety were also evaluated. Results From 2011 to 2013, 51 patients were enrolled (T, n = 32; TC, n = 19). Complete remission was observed in one patient with TC, partial response in five patients (T, n = 3; TC, n = 2), and stable disease in 38 patients (T, n = 27; TC, n= 11), with a DCR of 88% (T,: 93.8%; TC, 77.8%). With a median follow up of 25.7 months, median progression-free survival was 10.1 months (T,: 16.6 months; TC, 5.6 months), and median overall survival was 25.7 months (T, not reached; TC, 14.7 months). Fourteen patients had a serious drug-related adverse event; of these patients, nine permanently discontinued treatment. Three patients died of pneumonitis while in the study. Immunohistochemical positivity for p4E-BP1 or insulin-like growth factor-1 receptor was statistically significantly related to a shorter survival. Conclusion Everolimus may induce durable disease control in a high percentage of patients with T or TC, albeit with a potential high risk of fatal pneumonitis.
Bone Marrow Reticulin Fibrosis in 579 Patients with Polycythemia Vera and Essential Thrombocythemia: Effect on Clinical Outcome
Authors: Giulia Benevolo, Maura Nicolosi, Francesca Palandri, Laura Godio, Andrea Evangelista, Elena Crisà, Elena Sabattini, Barbara Nicolino, Ludovica Riera, Michele Cavo, Umberto Vitolo
Journal: Blood (2016)
Can we perform subtyping of non-small cell lung cancer patients by use of lung tissue metabolic fingerprinting?
Authors: M. Ciborowski, J. Kisluk, K. Pietrowska, P. Samczuk, E. Parfieniuk, T. Kowalczyk, M. Kozlowski, A. Kretowski, J. Niklinski
Journal: Annals of Oncology (2017)
Precision-cut liver slices as an ex-vivo model for human NAFLD show hepatic progenitor cell activation and fibrogenesis
Authors: O. Govaere, L.H. Reed, H. Brown, S.J. Cockell, J.J. French, S.A. White, D.M. Manas, A.K. Daly, S.M. Robinson, C. Griffiths, L.A. Borthwick, M.J. Drinnan, D. Tiniakos, Q.M. Anstee, F. Oakley
Journal: Journal of Hepatology (2017)
FXR agonists with sustained systemic rather than transient intestinal exposure are more efficacious in a diet-induced obese non-alcoholic steatohepatitis mouse model
Authors: B. Wagner, D. Brigham, K.-J. Lee, A. Ortiz, N. Lu, J. Qian, K. Douglas, J. Nagasawa, S. Govek, M. Feigh, S. Veidal, N. Vrang, K. Song, N. Smith
Journal: Journal of Hepatology (2017)
The impact of bariatric surgery on nonalcoholic fatty liver disease and cardiovascular risk utilizing non-invasive measures
Authors: C. Netanel, D. Goitein, M. Rubin, M. Shechter, Y. Kleinbaum, S. Katsherginsky, H. Hermon, R. Hemi, K. Tsaraf, A. Donuzi, M. Safran, I. Tachlytski, A. Herman, P. Ortiz, Z. Ben-Ari
Journal: Journal of Hepatology (2017)
Clinical course of patients with oxaliplatin-associated neuropathy: N08CB (Alliance).
Authors: Deirdre R. Pachman, Rui Qin, Drew K. Seisler, Ellen M. Lavoie Smith, Andreas S. Beutler, Lauren E. Ta, Jacqueline M. Lafky, Nina Wagner-Johnston, Kathryn Jean Ruddy, Shaker R. Dakhil, Axel Grothey, Charles L. Loprinzi
Journal: Journal of Clinical Oncology (2014)

3595 Background: Oxaliplatin is commonly associated with acute neuropathy, as well as a more troublesome chronic neurotoxicity. Details regarding the clinical course of these toxicities are not well defined. Methods: Acute and chronic oxaliplatin-induced peripheral neuropathy were evaluated in patients with colon cancer receiving adjuvant FOLFOX (fluorouracil, leucovorin, oxaliplatin) in a previously reported calcium/magnesium neuropathy prevention trial (Loprinzi JCO 2013). Acute neuropathy was assessed using daily questionnaires for 6 days starting with each cycle of FOLFOX. Chronic neurotoxicity was assessed using the EORTC QLQ-CIPN20 tool before each dose of oxaliplatin and at 1, 3, 6, 12, and 18 months after chemotherapy. Results: 89% of patients (308/346) had at least one acute neuropathy symptom (Sx) with the first cycle of FOLFOX: sensitivity to touching cold items (71%), sensitivity to swallowing cold items (71%), throat discomfort (63%), or muscle cramps (42%). Acute neuropathy Sx occurred within a day after oxaliplatin, peaked at day 3, then improved. These Sxs, however, did not resolve completely between treatments and were about twice as severe in cycles 2-12, than in cycle 1. Cycle 1 acute neuropathy Sx severity predicted acute Sx severity in subsequent cycles. Regarding the chronic neurotoxicity, tingling was the most severe Sx (1.91 out of 1-4), followed by numbness (1.72), and then pain (1.28). During chemotherapy, hand Sxs (1.70) were more prominent than feet Sxs (1.57). Following chemotherapy completion, sensory Sxs initially continued to worsen, on average, with improvement beginning approximately 3 months post-chemotherapy. By 18 months, residual numbness/tingling was more severe in feet than in hands. Patients with more severe acute neuropathy during the first cycle of therapy had more chronic sensory neurotoxicity (P<0.0001). Conclusions: Acute oxaliplatin-associated neuropathy Sxs do not completely resolve between treatment cycles and are only half as severe on the first cycle compared with subsequent cycles. There is a correlation between the severity of acute and chronic neuropathy. Hand Sxs are more severe during therapy, while feet symptoms become more prominent during follow up. Clinical trial information: NCT01099449.
YAP antagonizes innate antiviral immunity and is targeted for lysosomal degradation through IKKɛ-mediated phosphorylation
Authors: Shuai Wang, Feng Xie, Feng Chu, Zhengkui Zhang, Bing Yang, Tong Dai, Liang Gao, Lin Wang, Li Ling, Junling Jia, Hans van Dam, Jin Jin, Long Zhang, Fangfang Zhou
Journal: Nature Immunology (2017)
Cirrhosis impacts outcome of hemodialyzed patients and should lead to consider spontaneous liver-kidney transplantation
Authors: F. Artru, A. Louvet, F. Glowacki, S. Bellati, S. Gomis, H. Castel, J. Barthelon, G. Lassailly, S. Dharancy, M. Hazzan, P. Mathurin
Journal: Journal of Hepatology (2017)
Extracellular vesicles including microparticles from hepatitis B infected patients function as replication bodies and transmit HBV infection
Authors: S. Sukriti, M.C. Choudhary, S. Sharma, J.S. Maras, A. Singh, M. Islam, S. Sharma, N. Trehanpati, E. Gupta, S.K. Sarin
Journal: Journal of Hepatology (2017)
Preferential recognition of hepatitis B virus-DNA integrated target by hepatitis B virus-specific CD8 T cells
Authors: A. Khakpoor, Y. Ni, Z.Z. Ho, V. Oei, E.A. Felinska, N. Yang, J.X. Chow, C.T. Lim, S. Urban, A. Bertoletti
Journal: Journal of Hepatology (2017)
Acquisition of BTK C481S Produces Resistance to Ibrutinib in MYD88 Mutated WM and ABC DLBCL Cells That Is Accompanied By ERK1/2 Hyperactivation, and Is Targeted By the Addition of the ERK1/2 Inhibitor Ulixertinib
Authors: Jiaji G Chen, Xia Liu, Jie Chen, Lian Xu, Nicholas Tsakmaklis, Maria Demos, Christopher J Patterson, Jorge J. Castillo, Zachary Hunter, Steven P Treon, Guang Yang
Journal: Blood (2016)
Mucosal-associated invariant T lymphocytes are declined, activated, and exhausted in peripheral in chronic HBV-infected patients
Authors: Q. Liu, W.-W. Yin, Q.-F. Zhang, J.-Y. Shao, M.-H. Li, Y.-L. Li, H.-D. Hu, P. Hu, H. Ren, D.-Z. Zhang
Journal: Journal of Hepatology (2017)
A phase 2 study exploring once daily dosing of ritonavir boosted lonafarnib for the treatment of chronic delta hepatitis – end of study results from the LOWR HDV-3 study
Authors: C. Koh, P. Surana, T. Han, N. Fryzek, D. Kapuria, O. Etzion, V. Takyar, Y. Rotman, R. Canales, H. Dahari, C. Yurdaydin, J. Glenn, T. Heller
Journal: Journal of Hepatology (2017)
Clinical phenotype and outcome of hepatitis E virus associated neuralgic amyotrophy; an international retrospective comparative cohort study
Authors: K.J.E. Jones, J.J.J. Van Eijk, P. Ripellino, R.G. Madden, J. Herrod, R. Lissmann, G. Webb, M. Abdelrahim, H.H. Ashraf, O. Almasri, B.N.P. Mclean, C. Gobbi, D. Moradpour, T. Kuntzer, D. Benninger, M. Fraga, R. Sahli, J.M. Peron, H. Blasco-Perrin, J. Izopet, P. Colson, S. Attarian, R. Gerolami, J. Hartl, S. Pischke, M.T. Giordani, M. Fritz, M. Panning, R.P. Bendall, N. Lin, N. Van Alfen, B. Van Engelen, B.C. Jacobs, H.R. Dalton
Journal: Journal of Hepatology (2017)
Retreatment with Direct Active Antivirals of genotype 1, 3 and 4 chronic hepatitis C patients who previously failed an anti-NS5A-containing regimen in real world
Authors: P. Halfon, C. Scholtes, J. Izopet, S. Larrat, G. Penaranda, P. Trimoulet, F. Zoulim, L. Alric, S. Metivier, M. Bourliere, V. Leroy, D. Ouzan, V. de Ledinghen, S. Mohamed, M.-A. Thelu, F. Abravanel
Journal: Journal of Hepatology (2017)
Abstract A13: Macrophage FLT1 mediated inflammatory response determines breast cancer distal metastasis
Authors: Bin-Zhi Qian, Hui Zhang, Jiufeng Li, Eun-Jin Yeo, Neil O. Carragher, Anne R. Bresnick, Richard A. Lang, Jeffrey W. Pollard
Journal: Cancer Research (2016)

Abstract Macrophages are abundantly found in the tumor microenvironment and enhance malignancy. At distal metastatic sites, our previous studies identified a distinct population of metastasis associated macrophages (MAMs) that promotes tumor cell extravasation, seeding and persistent growth. These macrophages were derived from circulating inflammatory monocytes recruited by CCL2/CCR2 chemokine signaling and directly promote tumor cell extravasation and metastatic seeding in vivo through VEGF production. Our recent studies identified that MAMs express high levels of cell surface FMS-like tyrosine kinase 1 (FLT1, also known as VEGFR1) after their recruitment. Blockade of FLT1 signaling using specific inhibitory antibodies significantly inhibited the metastatic seeding and persistent growth. Using several genetic models of Flt1 deficiency, we show that macrophage specific FLT1 signaling is critical for breast tumor distal metastatic potential. FLT1 is not expressed by other hematopoietic cells and its inhibition did not affect the recruitment of MAMs, which indicated that specific FLT1 signaling in MAMs are important for their metastasis promoting functions. Indeed, we identified that FLT1 regulates a set of inflammatory response genes including Colony Stimulating Factor 1 (CSF1) a central regulator of macrophage biology. Using a genetic gain-of-function approach we show that CSF1 mediated autocrine signaling in MAMs is downstream of FLT1 and can restore the tumor-promoting activity in MAMs even when FLT1 has been inhibited. Together, our data established a link between inflammation and cancer metastasis and suggested the therapeutic potential of targeting these pathways in treating metastatic disease. Citation Format: Bin-Zhi Qian, Hui Zhang, Jiufeng Li, Eun-Jin Yeo, Neil O. Carragher, Anne R. Bresnick, Richard A. Lang, Jeffrey W. Pollard. Macrophage FLT1 mediated inflammatory response determines breast cancer distal metastasis. [abstract]. In: Proceedings of the AACR Special Conference on Tumor Metastasis; 2015 Nov 30-Dec 3; Austin, TX. Philadelphia (PA): AACR; Cancer Res 2016;76(7 Suppl):Abstract nr A13.
Correlates of resistance and relapse during blinatumomab therapy for relapsed/refractory acute lymphoblastic leukemia
Authors: Ibrahim Aldoss, Joo Song, Tracey Stiller, Tina Nguyen, Joycelynne Palmer, Margaret O'Donnell, Anthony S. Stein, Guido Marcucci, Stephen Forman, Vinod Pullarkat
Journal: American Journal of Hematology (2017)

Abstract We retrospectively analyzed 65 patients with refractory/relapsed (r/r) ALL who were treated with blinatumomab for predictors of leukemia response as well as clinical patterns of relapse and resistance with particular focus on downregulation of CD19 expression and extramedullary disease (EM‐ALL). The complete remission (CR) rate was 51%, and 15 (45%) responders underwent allogeneic hematopoietic cell transplantation (HCT) in CR. High leukemia burden (bone marrow blasts &gt;50%) ( P = .02), history of prior EM‐ALL ( P = .005), and active EM‐ALL at the time of initiating blinatumomab ( P = .05) predicted lower CR rate. Among refractory cases, 13 (41%) had evidence of EM‐ALL progression, and CD19 expression was negative or dim in 18% and 23%, respectively. Among responders, 20 (61%) subsequently relapsed among whom EM‐ALL relapse occurred in 8 (40%) patients, and CD19 expression was negative or dim in 35 and 6% of evaluable cases, respectively. Pretreatment moderate/strong CD19 expression ( P = .01) and history of prior EM‐ALL during ALL course ( P = .04) were risk factors for developing EM‐ALL at progression/relapse. However, no pretreatment factors predicted progression/relapse with CD19‐negative ALL. Overall‐survival (OS) and even‐free survival were improved for patients underwent allogeneic HCT compared to responders who did not. Furthermore, OS was superior for patients responded to blinatumomab compared to those who did not. Extramedullary and CD19‐negative disease are common during blinatumomab failure in r/r ALL. In addition to high leukemia burden, concurrent or prior history EM‐ALL were associated with lower response to blinatumomab. Higher CD19 expression as well as prior history of EM‐ALL were associated with EM‐ALL at the time of blinatumomab failure.