tbuckley/cabot-search huggingface dataset:
Effect of Postextubation High-Flow Nasal Cannula vs Noninvasive Ventilation on Reintubation and Postextubation Respiratory Failure in High-Risk Patients
Authors: Gonzalo Hernández, Concepción Vaquero, Laura Colinas, Rafael Cuena, Paloma González, Alfonso Canabal, Susana Sanchez, Maria Luisa Rodriguez, Ana Villasclaras, Rafael Fernández
Journal: JAMA (2016)

High-flow conditioned oxygen therapy delivered through nasal cannulae and noninvasive mechanical ventilation (NIV) may reduce the need for reintubation. Among the advantages of high-flow oxygen therapy are comfort, availability, lower costs, and additional physiopathological mechanisms.To test if high-flow conditioned oxygen therapy is noninferior to NIV for preventing postextubation respiratory failure and reintubation in patients at high risk of reintubation.Multicenter randomized clinical trial in 3 intensive care units in Spain (September 2012-October 2014) including critically ill patients ready for planned extubation with at least 1 of the following high-risk factors for reintubation: older than 65 years; Acute Physiology and Chronic Health Evaluation II score higher than 12 points on extubation day; body mass index higher than 30; inadequate secretions management; difficult or prolonged weaning; more than 1 comorbidity; heart failure as primary indication for mechanical ventilation; moderate to severe chronic obstructive pulmonary disease; airway patency problems; or prolonged mechanical ventilation.Patients were randomized to undergo either high-flow conditioned oxygen therapy or NIV for 24 hours after extubation.Primary outcomes were reintubation and postextubation respiratory failure within 72 hours. Noninferiority margin was 10 percentage points. Secondary outcomes included respiratory infection, sepsis, and multiple organ failure, length of stay and mortality; adverse events; and time to reintubation.Of 604 patients (mean age, 65 [SD, 16] years; 388 [64%] men), 314 received NIV and 290 high-flow oxygen. Sixty-six patients (22.8%) in the high-flow group vs 60 (19.1%) in the NIV group were reintubation (absolute difference, -3.7%; 95% CI, -9.1% to ∞); 78 patients (26.9%) in the high-flow group vs 125 (39.8%) in the NIV group experienced postextubation respiratory failure (risk difference, 12.9%; 95% CI, 6.6% to ∞) [corrected]. Median time to reintubation did not significantly differ: 26.5 hours (IQR, 14-39 hours) in the high-flow group vs 21.5 hours (IQR, 10-47 hours) in the NIV group (absolute difference, -5 hours; 95% CI, -34 to 24 hours). Median postrandomization ICU length of stay was lower in the high-flow group, 3 days (IQR, 2-7) vs 4 days (IQR, 2-9; P=.048). Other secondary outcomes were similar in the 2 groups. Adverse effects requiring withdrawal of the therapy were observed in none of patients in the high-flow group vs 42.9% patients in the NIV group (P < .001).Among high-risk adults who have undergone extubation, high-flow conditioned oxygen therapy was not inferior to NIV for preventing reintubation and postextubation respiratory failure. High-flow conditioned oxygen therapy may offer advantages for these patients.clinicaltrials.gov Identifier: NCT01191489.
CD45 Expression in Mitral Valve Endothelial Cells After Myocardial Infarction
Authors: Joyce Bischoff, Guillem Casanovas, Jill Wylie-Sears, Dae-Hee Kim, Philipp E. Bartko, J. Luis Guerrero, Jacob P. Dal-Bianco, Jonathan Beaudoin, Michael L. Garcia, Suzanne M. Sullivan, Margo M. Seybolt, Brittan A. Morris, Joshua Keegan, Whitney S. Irvin, Elena Aikawa, Robert A. Levine
Journal: Circulation Research (2016)

Ischemic mitral regurgitation, a complication after myocardial infarction (MI), induces adaptive mitral valve (MV) responses that may be initially beneficial but eventually lead to leaflet fibrosis and MV dysfunction. We sought to examine the MV endothelial response and its potential contribution to ischemic mitral regurgitation.Endothelial, interstitial, and hematopoietic cells in MVs from post-MI sheep were quantified. MV endothelial CD45, found post MI, was analyzed in vitro.Ovine MVs, harvested 6 months after inferior MI, showed CD45, a protein tyrosine phosphatase, colocalized with von Willebrand factor, an endothelial marker. Flow cytometry of MV cells revealed significant increases in CD45+ endothelial cells (VE-cadherin+/CD45+/α-smooth muscle actin [SMA]+ and VE-cadherin+/CD45+/αSMA- cells) and possible fibrocytes (VE-cadherin-/CD45+/αSMA+) in inferior MI compared with sham-operated and normal sheep. CD45+ cells correlated with MV fibrosis and mitral regurgitation severity. VE-cadherin+/CD45+/αSMA+ cells suggested that CD45 may be linked to endothelial-to-mesenchymal transition (EndMT). MV endothelial cells treated with transforming growth factor-β1 to induce EndMT expressed CD45 and fibrosis markers collagen 1 and 3 and transforming growth factor-β1 to 3, not observed in transforming growth factor-β1-treated arterial endothelial cells. A CD45 protein tyrosine phosphatase inhibitor blocked induction of EndMT and fibrosis markers and inhibited EndMT-associated migration of MV endothelial cells.MV endothelial cells express CD45, both in vivo post MI and in vitro in response to transforming growth factor-β1. A CD45 phosphatase inhibitor blocked hallmarks of EndMT in MV endothelial cells. These results point to a novel, functional requirement for CD45 phosphatase activity in EndMT. The contribution of CD45+ endothelial cells to MV adaptation and fibrosis post MI warrants investigation.
Most CCGs in England are failing to meet standards on cancer care
Authors: Gareth Iacobucci
Journal: BMJ (2016)

More than 85% of clinical commissioning groups (CCGs) in England are failing to meet national standards for diagnosing and treating cancer, new figures have shown.

NHS England’s first “Ofsted-style” ratings measuring performance on cancer care show that only seven of 209 CCGs (3%) received the highest rating of “top performing,” while a further 22 (11%) were judged to be “performing well.” Three quarters of CCGs (156) received a rating of “needs improvement,” while more than one in 10 (24) received the lowest rating of “greatest need for improvement.”

The lowest ranked group included six CCGs in London (Newham, City and Hackney, Tower Hamlets, Waltham Forest, Redbridge, and Haringey), plus …
miR-1298 Inhibits Mutant KRAS-Driven Tumor Growth by Repressing FAK and LAMB3
Authors: Ying Zhou, Jason Dang, Kung-Yen Chang, Edwin Yau, Pedro Aza-Blanc, Jorge Moscat, Tariq M. Rana
Journal: Cancer Research (2016)

Global miRNA functional screens can offer a strategy to identify synthetic lethal interactions in cancer cells that might be exploited therapeutically. In this study, we applied this strategy to identify novel gene interactions in KRAS-mutant cancer cells. In this manner, we discovered miR-1298, a novel miRNA that inhibited the growth of KRAS-driven cells both in vitro and in vivo Using miR-TRAP affinity purification technology, we identified the tyrosine kinase FAK and the laminin subunit LAMB3 as functional targets of miR-1298. Silencing of FAK or LAMB3 recapitulated the synthetic lethal effects of miR-1298 expression in KRAS-driven cancer cells, whereas coexpression of both proteins was critical to rescue miR-1298-induced cell death. Expression of LAMB3 but not FAK was upregulated by mutant KRAS. In clinical specimens, elevated LAMB3 expression correlated with poorer survival in lung cancer patients with an oncogenic KRAS gene signature, suggesting a novel candidate biomarker in this disease setting. Our results define a novel regulatory pathway in KRAS-driven cancers, which offers a potential therapeutic target for their eradication. Cancer Res; 76(19); 5777-87. ©2016 AACR.
Impact Of Residual Disease On Survival In Pediatric Patients Receiving Allogeneic Hematopoietic Cell Transplantation For Acute Myeloid Leukemia In First Complete Remission
Authors: John T. Horan, Soheil Meshinchi, Michael R. Loken, Todd A. Alonzo, Richard Aplenc, Stella M. Davies, Robert B. Gerbing, Alan S. Gamis
Journal: Blood (2013)
P2.01: LUME-MeSO: Phase II/III Study of Nintedanib + Pemetrexed/Cisplatin in Patients With Malignant Pleural Mesothelioma
Authors: Giorgio V. Scagliotti, Rabab Gaafar, Anna Nowak, Nicholas J. Vogelzang, Ute Von Wangenheim, Nassim Morsli, Derek Velema, Sanjay Popat
Journal: Journal of Thoracic Oncology (2016)
The association between time to recurrence after curative surgery and prognosis in stage III colorectal cancer
Authors: Kenjiro Tsuruoka, Natsuko Okita, Atsuo Takashima, Yoshitaka Honma, Satoru Iwasa, Ken Kato, Tetsuya Hamaguchi, Yasuhide Yamada, Yukihide Kanemitsu, Narikazu Boku
Journal: Annals of Oncology (2015)
Determination of efficacy of TIP combination (paclitaxel, ifosfamide, cisplatin) as first salvage therapy for patients with relapsed germ cell tumors in a poor prognosis group
Authors: J. Mardiak, K. Rejlekova, M. Mego, J. Rajec, Z. Sycova-Mila, J. Obertova, T. Salek, M. Reckova
Journal: Journal of Clinical Oncology (2009)

e16049 Background: The efficacy of TIP appears to be suitable salvage therapy for patients with relapsed germ cell tumors (GCTs) with good prognostic features.The aim of our study was to determine the efficacy of TIP as first salvage therapy for patients with relapsed GCTs with poor prognostic features. Methods: Thirty seven patients with relapsed GCTs were treated with TIP as first salvage therapy. Sixteen (43%) patients had favorable prognostic features for response (testis primary tumor site and prior complete response to induction chemotherapy regimen) and 21 (57%) patients had poor prognostic features (either extragonadal site or incomplete response to induction chemotherapy regimen). Four cycles of paclitaxel (175 to 250 mg/m 2 ), ifosfamide 6 g/m 2 , and cisplatin 100 mg/m 2 were given 21 days apart with GC-SF support, followed by resection of resectable radiographic residua. Results: Ten (69%) out of 16 patients with good prognostic features achieved a favorable response to TIP, and all 10 (100%) patients achieved complete response (CR). Six (60%) of the favorable responses remain durable at a median follow-up of 50,6 months. 9 (43%) of 21 patients with poor prognosis achieved a favorable response to chemotherapy, from whom only 1 (10%) patient achieved CR, but 5 patients achieved durable response at a median follow-up duration of 60,6 months. Estimated 2-year overall survival rate (OS) for patients with good prognosis was 56% (95 % CI 54–100%) and 33% (95% CI 21–68%) for patients with poor prognosis. Despite this results, estimated 5-year OS was even more positive for patients with poor prognosis 19% (95% CI 15–61%) comparing to 13% (95% CI 23–80%) for patients with good prognosis. Conclusions: Demonstrated long-term survival of patients with poor prognosis in our nonrandomised study with limited number of patients refers to the TIP being suitable therapy also for patients with relapsed GCTs with poor prognosis. These results warrant the need to continue investigation of real effectiveness of TIP as a first salvage therapy even for patients with poor prognostic features. No significant financial relationships to disclose.
Nintedanib plus pemetrexed/cisplatin followed by maintenance nintedanib for unresectable malignant pleural mesothelioma (MPM): An international, multicenter, randomized, double-blind, placebo-controlled phase II study.
Authors: Giorgio V. Scagliotti, Natasha B. Leighl, Anna K. Nowak, Nick Pavlakis, Sanjay Popat, Jens Benn Sorensen, Jose Barrueco, Rolf Kaiser, Arsene-Bienvenu Loembe, Martha Mueller, Ute von Wangenheim, Martin Reck
Journal: Journal of Clinical Oncology (2014)

TPS7612 Background: MPM is a rare cancer originating from multipotent mesothelial cells capable of differentiating into epithelial, sarcomatoid, or biphasic (mixed) neoplasms. The only approved 1st-line chemotherapeutic regimen for unresectable MPM, combination pemetrexed/cisplatin extends OS to only approximately one year, illustrating a need for improved treatment strategies. In the present trial, we are investigating the efficacy and safety of nintedanib (BIBF 1120) combined with pemetrexed/cisplatin for the treatment of unresectable MPM. Nintedanib is an oral, twice-daily, angiokinase inhibitor targeting most prominently vascular endothelial growth factor receptors 1–3, platelet-derived growth factor receptors α/β, and fibroblast growth factor receptors 1–3, as well as Src and Abl kinase signaling, which are involved in regulating tumor angiogenesis, growth, and metastasis of MPM. These signaling pathways are also implicated in the pathogenesis and maintenance of MPM. In previous studies, we demonstrated that nintedanib can be co-administered with various anti-cancer drugs to safely and significantly increase survival in patients (pts) with non-small cell lung cancer. Methods: A total of 86 pts—at least 18 years of age and with ECOG score of 0 or 1 and histologically confirmed epithelioid or biphasic MPM—will be randomized in a 1:1 ratio to receive either up to 6 cycles of 1st-line combination pemetrexed (500 mg/m2)/cisplatin (75 mg/m2) on day one administered along with nintedanib (200 mg bid) or placebo from days two to 21. Pts who do not develop progressive disease (PD) will continue to receive maintenance treatment with either nintedanib or placebo until PD. The primary endpoint is PFS. Secondary endpoints are OS and baseline change in forced vital capacity as a measure of pulmonary function. Frequency and severity of adverse events will also be evaluated as a measure of safety. All pts will attend an end-of-trial visit when they discontinue study treatment permanently, and return for follow-up visits until the end of trial, death, or loss to follow-up. Clinical trial information: NCT01907100.
MicroRNA-146a interferes with TCA cycle flux via DLST and rewires cardiomyocyte metabolism in hypertensive heart failure
Authors: Ward Heggermont, A. P Papageorgiou, Annelies Quaegebeur, Sophie Deckx, B Schroen, M Van Bilsen, Stefan Janssens, Y Pinto, Peter Carmeliet, Stephane Heymans
Journal: European Journal of Heart Failure (2014)
BCL2 Inhibition by Venetoclax: Targeting the Achilles' Heel of the Acute Myeloid Leukemia Stem Cell?
Authors: Vinod A. Pullarkat, Edward M. Newman
Journal: Cancer Discovery (2016)

Abstract Summary: Venetoclax is an oral drug with an excellent side-effect profile that has the potential to revolutionize acute myeloid leukemia (AML) therapy in two areas. Venetoclax-based combination therapies could be a bridge to hematopoietic cell transplant with curative intent for patients with refractory/relapsed AML, and venetoclax-based therapy could provide meaningful survival prolongation for older patients with AML who are not candidates for more aggressive therapies. Cancer Discov; 6(10); 1082–3. ©2016 AACR. See related article by Konopleva and colleagues, p. 1106.
Erratum: Corrigendum: Adjuvant-dependent innate and adaptive immune signatures of risk of SIVmac251 acquisition
Authors: Monica Vaccari, Shari N Gordon, Slim Fourati, Luca Schifanella, Namal P M Liyanage, Mark Cameron, Brandon F Keele, Xiaoying Shen, Georgia D Tomaras, Erik Billings, Mangala Rao, Amy W Chung, Karen G Dowell, Chris Bailey-Kellogg, Eric P Brown, Margaret E Ackerman, Diego A Vargas-Inchaustegui, Stephen Whitney, Melvin N Doster, Nicolo Binello, Poonam Pegu, David C Montefiori, Kathryn Foulds, David S Quinn, Mitzi Donaldson, Frank Liang, Karin Loré, Mario Roederer, Richard A Koup, Adrian McDermott, Zhong-Min Ma, Christopher J Miller, Tran B Phan, Donald N Forthal, Matthew Blackburn, Francesca Caccuri, Massimiliano Bissa, Guido Ferrari, Vaniambadi Kalyanaraman, Maria G Ferrari, DeVon Thompson, Marjorie Robert-Guroff, Silvia Ratto-Kim, Jerome H Kim, Nelson L Michael, Sanjay Phogat, Susan W Barnett, Jim Tartaglia, David Venzon, Donald M Stablein, Galit Alter, Rafick-Pierre Sekaly, Genoveffa Franchini
Journal: Nature Medicine (2016)
Cognitive behavioural therapy cuts GP visits by frequent attenders, finds study
Authors: Susan Mayor
Journal: BMJ (2016)

Cognitive behavioural therapy (CBT) is acceptable to long term frequent attenders and more than halved the frequency of their visits to primary care, a study has shown.

Most people who consult their GP frequently do so for only a limited time and return to normal consultation rates within 12 months. But a small group of patients, who typically have more than one long term condition and anxiety about their health, continue to attend frequently on a long term …
PAD Combination Therapy (PS-341/Bortezomib, Adriamycin and Dexamethasone) for Previously Untreated Patients with Multiple Myeloma.
Authors: James D. Cavenagh, Rakesh Popat, Nikki Curry, Jim Stec, Treen C. Morris, Mary Drake, Samir Agrawal, Patricia Smith, David P. Schenkein, Dixie-Lee Esseltine, Heather Oakervee
Journal: Blood (2004)
Impact of Intracoronary Cell Therapy on Left Ventricular Function in the Setting of Acute Myocardial Infarction, A Collaborative Meta-analysis of Randomized Controlled Clinical Trials
Authors: Ronak Delewi, Alexander Hirsch, Jan Tijssen, Volker Schaechinger, Wojciech Wojakowski, Jerome Roncalli, Svend Aakhus, Sandra Erbs, Birgit Assmus, Michal Tendera, Patricia Lemarchand, Ketil Lunde, Feng Cao, Heikki Huikuri, Stefan Janssens, Kai Wollert, Michal Plewka, Stefan Grajek, Jay Traverse, Felix Zijlstra, Jan Piek
Journal: Circulation (2012)
The effect of zoledronic acid on the prevention of bone loss in lymphoma patients receiving first-line therapy.
Authors: J. R. Westin, F. B. Hagemeister, M. A. Thompson, V. D. Cataldo, B. B. Toth, P. Sanjorjo, S. Bourgeois, C. Jimenez, W. A. Murphy, L. W. Kwak, M. D. Anderson Department of Lymphoma/Mye
Journal: Journal of Clinical Oncology (2010)

9103 Background: The majority of lymphoma patients receiving first-line chemotherapy have osteopenia, and risk of further bone loss increases with alkylating agent or corticosteroid treatment. Zoledronic acid, a potent bisphosphonate, has not been evaluated in lymphoma patients. Urine NTx and bone specific alkaline phosphatase (BSAP) are surrogate markers of bone turnover, and we have previously reported their value in early prediction of bone density outcomes. We conducted a randomized phase III trial to determine if zoledronic acid reduces the risk of bone mineral density (BMD) loss in this patient population. Methods: All patients with newly diagnosed lymphoma were evaluated from 2005 to 2009. Exclusion criteria included baseline osteoporosis, recent steroid or bisphosphonate use, or serious concurrent illness. Patients received randomized therapy of either: 1) oral calcium and vitamin D (Ca + D), or 2) Ca + D and 4 mg zoledronic acid intravenously at baseline and at 6 months. Results: To date, 42 patients have completed the study and have evaluable data. Patient characteristics included 23 men; 4 pre-menopausal women; and median age of 61 years (range 33-80 years). Twenty patients had mild osteopenia in at least one measured site upon enrollment. The baseline BMD was similar in the both groups. Patients who received zoledronic acid had stable median T-scores during the 12-month observation, whereas the T-scores of the control group decreased at every location evaluated (p value = L1-L4: 0.017, Left Neck: 0.08, Left Hip: 0. 312, Right Neck: 0.021, Right Hip: 0.118). We found that urine NTx and BSAP were statistically different between the groups at 3 months, and remained so through 12 months (NTx: 3 month p<0.001, 12 month p<0.001; BSAP: 3 month p=0.001, 12 month p<0.001). Conclusions: Treatment with zoledronic acid in patients with newly diagnosed lymphoma effectively prevents the BMD loss seen in this population. Urine NTx and BSAP predict early response to bisphosphonates, which may allow for early intervention, potentially preventing further bone loss. Bone mass loss is difficult to restore, thus requiring effective prevention strategies. Additional studies should be conducted to confirm these findings. Author Disclosure Employment or Leadership Position Consultant or Advisory Role Stock Ownership Honoraria Research Funding Expert Testimony Other Remuneration Novartis
Short Communication: PPARγ Mediates a Direct Antiangiogenic Effect of ω3-PUFAs in Proliferative Retinopathy
Authors: Andreas Stahl, Przemyslaw Sapieha, Kip M. Connor, John Paul SanGiovanni, Jing Chen, Christopher M. Aderman, Keirnan L. Willett, Nathan M. Krah, Roberta J. Dennison, Molly R. Seaward, Karen I. Guerin, Jing Hua, Lois E.H. Smith
Journal: Circulation Research (2010)

Omega3 long-chain polyunsaturated fatty acids (omega3-PUFAs) are powerful modulators of angiogenesis. However, little is known about the mechanisms governing omega3-PUFA-dependent attenuation of angiogenesis.This study aims to identify a major mechanism by which omega3-PUFAs attenuate retinal neovascularization.Administering omega3-PUFAs exclusively during the neovascular stage of the mouse model of oxygen-induced retinopathy induces a direct neovascularization reduction of more than 40% without altering vasoobliteration or the regrowth of normal vessels. Cotreatment with an inhibitor of peroxisome proliferator-activated receptor (PPAR)gamma almost completely abrogates this effect. Inhibition of PPARgamma also reverses the omega3-PUFA-induced reduction of retinal tumor necrosis factor-alpha, intercellular adhesion molecule-1, vascular cell adhesion molecule-1, endothelial selectin, and angiopoietin 2 but not vascular endothelial growth factor.These results identify a direct, PPARgamma-mediated effect of omega3-PUFAs on retinal neovascularization formation and retinal angiogenic activation that is independent of vascular endothelial growth factor.
TP53 Mutation Status Divides MDS Patients with Complex Karyotypes into Distinct Prognostic Risk Groups: Analysis of Combined Datasets from the International Working Group for MDS-Molecular Prognosis Committee
Authors: Rafael Bejar, Elli Papaemmanuil, Torsten Haferlach, Guillermo Garcia-Manero, Jaroslaw P. Maciejewski, Mikkael A. Sekeres, Matthew J. Walter, Timothy A. Graubert, Mario Cazzola, Luca Malcovati, Peter J Campbell, Seishi Ogawa, Jacqueline Boultwood, David Bowen, Sudhir Tauro, Michael J Groves, Michaela Fontenay, Lee-Yung Shih, Heinz Tüchler, Kristen E. Stevenson, Donna Neuberg, Peter L. Greenberg, Benjamin L. Ebert
Journal: Blood (2014)