tbuckley/cabot-search huggingface dataset:
P59 Factors influencing step-up to lama+laba/ics in COPD patients initially on lama monotherapy: a thin database study
Authors: JR Hurst, M Dilleen, K Morris, S Hills, B Emir, R Jones
Journal: Thorax (2016)

<h3></h3> The potentially inappropriate use of inhaled long-acting beta agonist/corticosteroid (LABA/ICS) combinations in COPD patients for whom this treatment is not recommended has clinical and economic implications. This retrospective analysis of anonymized electronic medical records in the UK Health Improvement Network (THIN) database was conducted to identify factors associated with step-up from long-acting muscarinic antagonist (LAMA) to LAMA+LABA/ICS therapy. Secondary objectives included time to step-up, Global Initiative for Chronic Obstructive Lung Disease (GOLD) and Medical Research Council (MRC) classification. Data were included from COPD patients between 1 June 2010 and 4 September 2014, aged ≥35 years at first LAMA treatment, with continuous enrolment &gt;360 days before the index event (date of first LAMA prescription) who received LAMA monotherapy only prior to step-up. Time to step-up was analysed using a Cox regression model with time-varying covariates using a stepwise model selection procedure. Data from 8773 patients (6199 LAMA [136 deaths]; 2438 LAMA+LABA/ICS) were included. Multivariable analysis revealed that exacerbations (composite), elective secondary care contact, markers of COPD proactive planned care, and reactive COPD care within the primary care setting were clinically and statistically significantly associated with step-up. Statistically significant factors negatively associated with step-up were being female and having diabetes (Table). Univariate analysis revealed FEV1, COPD severity and MRC classification to be significant predictors of step-up. These were not included in the multivariable model due to reduced observations, but sensitivity analyses including each in turn confirmed the above predictors. 28% of the cohort received step-up therapy, the majority (23%) within 2 years of LAMA monotherapy initiation. Assessment per GOLD classification suggests that step-up was appropriate in most patients (group A, 18%; B, 21%; C, 26%; D, 35%). Assessment of MRC score (mean, median) in the step-up group (baseline: 2.45, 2.00; follow-up: 2.74, 3.00) suggests that patients who were stepped-up became more symptomatic prior to step-up. These results show that COPD exacerbations were the most significant predictor of therapy step-up and that patients with initially stable disease are unlikely to require step-up. Therapy step-up appears to be appropriate in the majority of, but not all patients, and may reflect adherence to national guidelines.
A Phase I Study of Immune Gene Therapy for Patients with CLL Using Intranodal Injection of ISF35, a Membrane-Stable CD40 Binding Protein.
Authors: Januario Castro, Jose D. Sandoval, Johanna Melo-Cardenas, Denise Darrah, Mauricio Urquiza, Charles Prussak, Thomas J. Kipps
Journal: Blood (2008)
Elder abuse prevalence in community settings: a systematic review and meta-analysis
Authors: Yongjie Yon, Christopher R Mikton, Zachary D Gassoumis, Kathleen H Wilber
Journal: The Lancet Global Health (2017)

BackgroundElder abuse is recognised worldwide as a serious problem, yet quantitative syntheses of prevalence studies are rare. We aimed to quantify and understand prevalence variation at the global and regional levels.MethodsFor this systematic review and meta-analysis, we searched 14 databases, including PubMed, PsycINFO, CINAHL, EMBASE, and MEDLINE, using a comprehensive search strategy to identify elder abuse prevalence studies in the community published from inception to June 26, 2015. Studies reporting estimates of past-year abuse prevalence in adults aged 60 years or older were included in the analyses. Subgroup analysis and meta-regression were used to explore heterogeneity, with study quality assessed with the risk of bias tool. The study protocol has been registered with PROSPERO, number CRD42015029197.FindingsOf the 38 544 studies initially identified, 52 were eligible for inclusion. These studies were geographically diverse (28 countries). The pooled prevalence rate for overall elder abuse was 15·7% (95% CI 12·8–19·3). The pooled prevalence estimate was 11·6% (8·1–16·3) for psychological abuse, 6·8% (5·0–9·2) for financial abuse, 4·2% (2·1–8·1) for neglect, 2·6% (1·6–4·4) for physical abuse, and 0·9% (0·6–1·4) for sexual abuse. Meta-analysis of studies that included overall abuse revealed heterogeneity. Significant associations were found between overall prevalence estimates and sample size, income classification, and method of data collection, but not with gender.InterpretationAlthough robust prevalence studies are sparse in low-income and middle-income countries, elder abuse seems to affect one in six older adults worldwide, which is roughly 141 million people. Nonetheless, elder abuse is a neglected global public health priority, especially compared with other types of violence.FundingSocial Sciences and Humanities Research Council of Canada and the WHO Department of Ageing and Life Course.
P3.02b-095 Tracing Spatiotemporal T790M Heterogeneity in Patients with EGFR-Mutant Advanced NSCLC after Acquired Resistance to EGFR TKIs
Authors: Yi-Chen Zhang, Can Pi, E-E Ke, Zhi-Hong Chen, Jian Su, Zhong-Yi Dong, Chong-Rui Xu, Hai-Yan Tu, Hong-Hong Yan, Wen-Zhao Zhong, Jin -Ji Yang, Xu-Chao Zhang, Yi Long Wu, Qing Zhou
Journal: Journal of Thoracic Oncology (2017)
The Effect of Transplant Center Characteristics On Survival After Pediatric Hematopoietic Cell Transplantation
Authors: Michael J Eckrich, Jennifer Le-Rademacher, J. Douglas Rizzo, K. Scott Baker, Deepika Bhatla, David K. Buchbinder, Kenneth R. Cooke, Reggie Duerst, Andrew Gilman, Haydar Frangoul, Neena Kapoor, Nancy A. Kernan, Michael Verneris, Mary Eapen
Journal: Blood (2012)
P3.04-030 Examination of the Relevance of Prolonged Air Leakage after Pulmonary Resection for Lung Cancer and Factors Affecting Delayed Wound Healing
Authors: Koshi Nagano, Kiyotoshi Inoue, Hikaru Miyamoto, Shinjiro Mizuguchi, Noritoshi Nishiyama
Journal: Journal of Thoracic Oncology (2017)
The Roles of Alcohol and Drugs in Firearm Violence
Authors: Emma E. McGinty, Daniel W. Webster
Journal: JAMA Internal Medicine (2017)

Our website uses cookies to enhance your experience. By continuing to use our site, or clicking "Continue," you are agreeing to our Cookie Policy | Continue JAMA Internal Medicine HomeNew OnlineCurrent IssueFor Authors Podcast Publications JAMA JAMA Network Open JAMA Cardiology JAMA Dermatology JAMA Health Forum JAMA Internal Medicine JAMA Neurology JAMA Oncology JAMA Ophthalmology JAMA Otolaryngology–Head & Neck Surgery JAMA Pediatrics JAMA Psychiatry JAMA Surgery Archives of Neurology & Psychiatry (1919-1959) JN Learning / CMESubscribeJobsInstitutions / LibrariansReprints & Permissions Terms of Use | Privacy Policy | Accessibility Statement 2023 American Medical Association. All Rights Reserved Search All JAMA JAMA Network Open JAMA Cardiology JAMA Dermatology JAMA Forum Archive JAMA Health Forum JAMA Internal Medicine JAMA Neurology JAMA Oncology JAMA Ophthalmology JAMA Otolaryngology–Head & Neck Surgery JAMA Pediatrics JAMA Psychiatry JAMA Surgery Archives of Neurology & Psychiatry Input Search Term Sign In Individual Sign In Sign inCreate an Account Access through your institution Sign In Purchase Options: Buy this article Rent this article Subscribe to the JAMA Internal Medicine journal
Redundant Mechanisms for Dendritic Cell Activation in GVHD Induction: Signalings Via TLRs, TNF-α, IL-1 and CD40 Are Not Required
Authors: Hongmei Li, Catherine Matte-Martone, Anthony Jake Demetris, Jennifer McNiff, Dhanpat Jain, Warren D. Shlomchik
Journal: Blood (2008)
Daunorubicin or Not During the Induction Treatment of Childhood Standard-Risk B-Cell Precursor Acute Lymphoblastic Leukemia (SR-BCP-ALL): The Randomized Fralle 2000-A Protocol
Authors: Andre Baruchel, Arnaud Petit, Thierry Leblanc, Gérard Michel, Yves Perel, Francoise Mechinaud, Virginie Gandemer, Claudine Schmitt, Pascale Schneider, Benoit Brethon, Anne Auvrignon, Caroline Thomas, Geneviève Margueritte, Christiane Vermylen, Odile Lejars, Isabelle Pellier, Claire Berger, Gérard Couillault, Catherine Paillard, Christian Berthou, Christophe Piguet, Brigitte Pautard, Jean Soulier, Nathalie Grardel, Kheira Beldjord, Marie-Francoise Auclerc, Elizabeth Macintyre, Jean-Michel Cayuela, Sylvie Chevret, Guy Leverger
Journal: Blood (2012)
Biodegradable nanoparticle delivery of inactivated swine influenza virus vaccine provides heterologous cell-mediated immune response in pigs
Authors: Santosh Dhakal, Jagadish Hiremath, Kathryn Bondra, Yashavanth S Lakshmanappa, Duan-Liang Shyu, Kang Ouyang, Kyung-il Kang, Basavaraj Binjawadagi, Jonathan Goodman, Kairat Tabynov, Steven Krakowka, Balaji Narasimhan, Chang Won Lee, Gourapura J. Renukaradhya
Journal: Journal of Controlled Release (2017)
P1.04-002 Positive Airway Pressure-Enhanced CT to Improve Virtual Bronchoscopic Navigation
Authors: Marta Diez-Ferrer, Debora Gil, Elena Carreño, Susana Padrones, Samantha Aso, Vanesa Vicens, Noelia Cubero, Rosa Lopez-Lisbona, Carles Sanchez, Agnes Borras, Jordi Dorca, Antoni Rosell
Journal: Journal of Thoracic Oncology (2017)
Generation of human immune responses towards membrane macrophage colony stimulating factor (mM-CSF) expressing U251 glioma cells within immunodeficient (NIH-nu/beige/xid) mice
Authors: Harold Wepsic, Christina Delgado, Neil Hoa, Patric Schiltz, Reza Jahroudi, Jian Zhang, Martin Jadus
Journal: Cancer Research (2007)

1864  We investigated both in vitro and in vivo how human peripheral blood mononuclear cells (PBMC) respond towards cloned human HLA-A2+ U251 glioma cells (U251-2F11/TK) expressing membrane macrophage colony stimulating factor (mM-CSF). Enriched human monocytes derived from cancer patients specifically produced a respiratory burst within 20 minutes of interacting with mM-CSF expressing U251 glioma cells, but not with the viral vector control U251 (U251-VV) cells. Reactive oxygen species such as H2O2 and HOCl killed the U-251 cells. The U251-2F11/TK cells failed to grow within severe combined immunodeficient (NIH-bg-nu-xidBR) mice that were depleted of murine monocyte/macrophages but reconstituted with human HLA-A2+ PBMC (4 of 4). Reactive oxygen species were produced both in vitro and in vivo when the PBMC responded to the mM-CSF expressing U251 cells. U251-2F11/TK cells failed to form lasting subcutaneous tumors in all the mouse-macrophage depleted mice (0 of 4) that were reconstituted with human PBMC; whereas, the U251-VV cells progressively grew. From our work we conclude that mM-CSF transduced U251-2F11/TK glioma cells can safely stimulate human immune responses in vivo.
In vivo tumor growth inhibition by novel PKM2 cancer metabolism modulators.
Authors: O. M. Becker, V. Behar, O. Bohana-Kashtan, A. Shitrit, D. Sherman, E. Ben-Zeev, R. Ozeri, N. C. Schutz, A. Yacovan
Journal: Journal of Clinical Oncology (2011)

10530 Background: Cancer cells undergo major metabolic changes to enable efficient conversion of glucose needed for cell growth and proliferation. This phenomenon, which takes place even when oxygen is abundant, is known as the Warburg effect. A key mediator of this effect is pyruvate kinase (PK), a rate-limiting enzyme that catalyzes the last step in glycolysis. PK subtype M2 (PKM2), which is over expressed in cancer cells, facilitates the Warburg effect by switching from a highly active tetrameric form to low activity monomeric or dimeric forms. Thus small molecule PKM2 activators that stabilize the tetrameric form are expected to renormalize cancer metabolism, offering a novel therapeutic strategy. Methods: Novel PKM2 activators were discovered using a structure-based approach, and tested in multiple in vitro and in vivo studies. Results: Several series of novel, potent, allosteric PKM2 activators with AC50s as low as 20nM were discovered. By stabilizing the active tetrameric form of PKM2 more than 10-fold, these activators lower the levels of lactate in cancer cells, thus countering the Warburg effect. In cellular assays, these compounds significantly reduce the proliferation rate of multiple cancer cell lines, representing 5 different tumor types (colorectal, renal, lung, cervix, liver). So far, the greatest sensitivity was observed in colorectal cancer (CRC) and renal cell carcinoma (RCC) cell lines. Combination with commonly used chemotherapeutic agents show an additive, and in some cases a slight synergistic, effect on cells. In in vivo mouse xenograft models with the CRC cell line HT29, even a modestly active compound, such as DNX-03013 (AC50=0.9uM), demonstrated within a few days of treatment tumor growth inhibition greater than 50% (200 and 400 mg/kg IP QD). The compound was safe in mouse even at high exposure levels (400 mg/kg IP QD), indicating that these efficacious doses are significantly below the MTD. Conclusions: Taken together, this is the first report of potent PKM2 novel small-molecule cancer metabolism modulators that show promising anti-cancer therapeutic potential in vivo. The favorable DMPK profile of these compounds suggests that they can be further developed either as mono-therapy or as combination therapy.
Toward chronic hepatitis C eradication in HIV-positive patients, including those cirrhotic and infected with genotype 3 viruses
Authors: Amélie Menard, Sarah Aherfi, Saadia Mokhtari, Catherine Dhiver, Isabelle Ravaux, Hervé Tissot-Dupont, Line Meddeb, Philippe Brouqui, Andreas Stein, Philippe Colson
Journal: Gut (2017)

Direct-acting agents (DAA) have proved dramatic efficiency to cure chronic hepatitis C.1 ,2 Extensive assessment of their real-life effectiveness is now required, including in cirrhotic and genotype 3 HCV-infected patients who are under-represented in real-world studies but are considered the still hard-to-cure population.1–5 We read therefore with interest the article by Welzel et al 1 about the achievement of sustained virological response (SVR) in 91% of cases in a real-world cohort treated with sofosbuvir plus daclatasvir with or without ribavirin for 12–24 weeks. Indeed, remarkably, SVR was 92% in patients infected with HCV-3 (n=102), 97% in cirrhotics (n=389), 98% in HIV-infected individuals (n=55) and 96% in case of prior HCV therapy (n=341).

We analysed the efficacy and safety of DAA-based anti-HCV therapies administered during 2 years (May 2014–April 2016) to a real-world cohort of 170 HCV-HIV-coinfected …
P282 Comparitive use of nhanes III, ECCS and GLI prediction equations in determining spirometric indices and suitability for anti-fibrotic therapy in patients with idiopathic pulmonary fibrosis
Authors: I Cliff, A Ali, M Spiteri, H Stone
Journal: Thorax (2016)

<h3>Introduction</h3> Prediction equations are used to assess disease severity and prognosis in respiratory disease; globally most laboratories utilise ECCS or NHANES III equations. The Global Lung Initiative (GLI) produced reference ranges for spirometry that are multi-ethnic and applicable for patients upto the age of 95. The choice of which equation to use becomes crucial in idiopathic pulmonary fibrosis [IPF] patients, in whom prescription of currently available anti-fibrotic agents, Nintedanib and Pirfenidone is dependent on a forced vital capacity [FVC] between 50 and 80% of predicted in England and Wales (Scotland only restriction is FVC above 80% predicted). <h3>Methods</h3> Spirometric data recorded on 132 IPF patients were extracted from our BTS ILD Registry database. Values for FVC% predicted were calculated using the ECCS, NHANES III and GLI equations and compared to determine patient eligibility for anti-fibrotic treatment in line with published NICE Guidance. <h3>Results</h3> Data on 132 consecutive patients is presented in Table 1. This demonstrates the FVC% predicted when the 3 separate equations are used. At our centre, where ECCS is routinely used to calculate FVC% predicted, 62 patients (47%) of patients had an FVC above the upper limit of the treatment threshold of 80%. Of this group, 8 had evidence of more than 25% emphysematous change on their HRCT scans. <h3>Conclusions</h3> Using ECCS, 50% of patients met the NICE criteria for anti-fibrotic treatment. When NHANES III and GLI are used, patient eligibility for treatment increases to 61% and 59% respectively. Interestingly both the NHANES and GLI equations decrease the % predicted, and those patients that are just above the 80% cut off when ECCS is used become eligible for treatment just by using alternative prediction equations. The NICE Guidance does not specify which equation to use when assessing patients; in our patient cohort, the NHANES III or GLI would allow more patients to meet NICE eligibility for treatment. These data question, the use of predictive FVC cut-offs in prescribing anti-fibrotic treatments in a progressive lung disease without providing a national reference standard, especially when the particular prediction equation used could significantly impact on patients’ eligibility for treatment.
The PNPLA3 I148M variant modulates the fibrogenic phenotype of human hepatic stellate cells
Authors: Francesca Virginia Bruschi, Thierry Claudel, Matteo Tardelli, Alessandra Caligiuri, Thomas M. Stulnig, Fabio Marra, Michael Trauner
Journal: Hepatology (2017)

The genetic polymorphism I148M of patatin-like phospholipase domain-containing 3 (PNPLA3) is robustly associated with hepatic steatosis and its progression to steatohepatitis, fibrosis, and cancer. Hepatic stellate cells (HSCs) are key players in the development of liver fibrosis, but the role of PNPLA3 and its variant I148M in this process is poorly understood. Here we analyzed the expression of PNPLA3 during human HSC activation and thereby explored how a PNPLA3 variant impacts hepatic fibrogenesis. We show that expression of PNPLA3 gene and protein increases during the early phases of activation and remains elevated in fully activated HSCs (P < 0.01). Knockdown of PNPLA3 significantly decreases the profibrogenic protein alpha-smooth muscle actin (P < 0.05). Primary human I148M HSCs displayed significantly higher expression and release of proinflammatory cytokines, such as chemokine (C-C motif) ligand 5 (P < 0.01) and granulocyte-macrophage colony-stimulating factor (P < 0.001), thus contributing to migration of immune cells (P < 0.05). Primary I148M HSCs showed reduced retinol (P < 0.001) but higher lipid droplet content (P < 0.001). In line with this, LX-2 cells stably overexpressing I148M showed augmented proliferation and migration, lower retinol, and abolished retinoid X receptor/retinoid A receptor transcriptional activities but more lipid droplets. Knockdown of I148M PNPLA3 (P < 0.001) also reduces chemokine (C-C motif) ligand 5 and collagen1α1 expression (P < 0.05). Notably, I148M cells display reduced peroxisome proliferator-activated receptor gamma transcriptional activity, and this effect was attributed to increased c-Jun N-terminal kinase, thereby inhibiting peroxisome proliferator-activated receptor gamma through serine 84 phosphorylation and promoting activator protein 1 transcription. Conversely, the c-Jun N-terminal kinase inhibitor SP600125 and the peroxisome proliferator-activated receptor gamma agonist rosiglitazone decreased activator protein 1 promoter activity.These data indicate that PNPLA3 is required for HSC activation and that its genetic variant I148M potentiates the profibrogenic features of HSCs, providing a molecular mechanism for the higher risk of progression and severity of liver diseases conferred to patients carrying the I148M variant. (Hepatology 2017;65:1875-1890).
Loss of the Y Chromosome in MDS - Age-Related Phenomenon or Clonal Abnormality?
Authors: Christina Ganster, Friederike Braulke, Katayoon Shirneshan, Francesc Solé, Mar Mallo, Jose Cervera, Elisa Luño, Barbara Hildebrandt, Christian Steidl, Christa Fonatsch, Michael Pfeilstöcker, Thomas Nösslinger, Peter Valent, Aristoteles Giagounidis, Carlo Aul, Michael Lübbert, Reinhard Stauder, Otto Krieger, Michelle M. Le Beau, John M. Bennett, Peter L. Greenberg, Ulrich Germing, Detlef Haase, Julie Schanz
Journal: Blood (2010)
Fulvestrant (F) and letrozole (L) combination in second-line or more for estrogen receptor (ER)-positive (+) metastatic breast cancer (MBC): Efficacy and predictive factors of response.
Authors: A. M. Obermiller, M. S. Copur, M. Bolton, R. C. Ramaekers, R. Hays, D. Nelson, H. Benzel, M. Mickey, M. Norvell, J. Olsen, M. Tharnish, B. Luebbe, S. Schneider, S. Woodward, B. Keenportz, S. Frankforter, L. Mlinar
Journal: Journal of Clinical Oncology (2011)

e11137 Background: Preclinical data show that complete estrogen blockade, by down regulating ER and inhibiting estrogen synthesis, has greater effect on tumor growth than either treatment alone. Combination of an aromatase inhibitor (AI) and F may be an optimal second-line therapy by preventing activation of growth factor pathways and possible cross talk with ER. One clinical study has shown no benefit of adding anastrozole (A) to F at first relapse. No clinical data on combination L and F in the second line or more MBC is available. Methods: ER+, progesterone receptor(PgR) + or negative (-) MBC patients (pts) with prior chemo and/or non-AI endocrine(E) therapy were treated with L and F. Pts with complete/partial response, or stable disease were considered to have clinical benefit (CR+PR+SD). The predictive effect of age, number of prior regimens, ER/PgR status, and lobular histology were examined using Chi-square test. Results: 32 pts received L (2.5 mg/d po) plus F (250 mg/month, im). Mean age was 70 (Range: 35-92), median number of prior treatments was 2 (range1-6). 25 pts had ER+/PgR+, 7 pts had ER+/PgR- tumors. 25 pts had prior non-AI E therapy. 8 pts had lobular histology. Overall clinical benefit rate was 71% (3 CR, 7 PR, 13 SD). Mean duration of the clinical benefit was 15 months (range 2-38). 8 pts progressed under therapy. Age > 65 vs younger (89% vs 46%, p=0.007), prior treatments< 4 vs more (87% vs 25%, p=0.0007) and ER+/PgR+ vs ER+/PgR- (84% vs 42%, p<0.05) were predictive of clinical benefit; lobular histology and prior E therapy did not have any effect on clinical benefit (p>0.05). Conclusions: In pretreated MBC, combination of L and F can be effective with mean clinical benefit duration of 15 months. Older age, < 4 prior lines of therapy, and expression of both ER/PgR are predictive of clinical benefit while lobular histology and prior E therapy are not. L and F combination can be a reasonable option in selected group of MBC pts and should be further evaluated in larger studies using high dose F schedule.