tbuckley/cabot-search huggingface dataset:
Target Expression, Preclinical Activity and Mechanism of Action of EM801: A Novel First-in-Class Bcma T-Cell Bispecific Antibody for the Treatment of Multiple Myeloma
Authors: Anja Seckinger, Jose Antonio Delgado, Laura Moreno, Brigitte Neuber, Anna Grab, Susanne Lipp, Juana Merino, Minh Diem Vu, Klaus Strein, Felipe Prosper, Michael Hundemer, Jesus San Miguel, Dirk Hose, Bruno Paiva
Journal: Blood (2015)
Randomized Phase 2 Open-Label Study of R-CHOP ± Bortezomib in Patients (Pts) with Untreated Non-Germinal Center B-Cell-like (Non-GCB) Subtype Diffuse Large Cell Lymphoma (DLBCL): Results from the Pyramid Trial (NCT00931918)
Authors: John P. Leonard, Kathryn Kolibaba, James A. Reeves, Anil Tulpule, Ian W. Flinn, Tatjana Kolevska, Robert Robles, Christopher Flowers, Robert Collins, Nicholas J. DiBella, Steven W. Papish, Parameswaran Venugopal, Andrew Horodner, Amir Tabatabai, Julio Hajdenberg, George Mulligan, Rachel Neuwirth, Kaveri Suryanarayan, Dixie-Lee Esseltine, Sven de Vos
Journal: Blood (2015)
Overall survival results from a phase III study of tivozanib hydrochloride versus sorafenib in patients with renal cell carcinoma.
Authors: Robert John Motzer, Timothy Eisen, Thomas E. Hutson, Cezary Szczylik, Mizue Krygowski, Andrew Louis Strahs, Brooke Esteves, Andrew P. Krivoshik, Anna Berkenblit, Dmitry Nosov
Journal: Journal of Clinical Oncology (2013)

350 Background: Tivozanib hydrochloride (tivozanib) is a potent, selective, tyrosine kinase inhibitor targeting all three vascular endothelial growth factor receptors, with a long half-life. Tivozanib has shown tolerability and superior progression-free survival and overall response rate versus sorafenib in a phase III trial (TIVO-1) in patients with advanced renal cell carcinoma. Final overall survival (OS) data (August 27, 2012) from TIVO-1 and its open-label, multicenter extension study are reported. Methods: A total of 517 patients were randomized 1:1 to tivozanib 1.5 mg/d (3 weeks on, 1 week off) or sorafenib 400 mg/d (twice a day, continuously) (J Clin Oncol2012;30[suppl]:Abstract 4501). In the extension study, patients who progressed (PD) on sorafenib based on investigator assessment were eligible to receive tivozanib, and patients with PD on tivozanib received subsequent treatment according to regional standards of care. Final OS analysis was planned to be conducted after all patients had died or were lost to follow-up, or when all patients in follow-up had been on study for at least 2 years, whichever occurred first. OS was compared using the stratified log-rank test. OS distribution was estimated using the Kaplan-Meier method. Hazard ratio (HR) was estimated using the Cox proportional hazard regression model. Results: At the time of final OS analysis (2 years after last patient was enrolled), 219 deaths had occurred (tivozanib, n=118 [45.4%]; sorafenib, n=101 [39.3%]) (stratified HR=1.245; 95% confidence interval [CI] 0.954–1.624; p=0.105), trending in favor of the sorafenib arm. Median OS (95% CI) was 28.8 months (22.5–NA) for tivozanib and 29.3 months (29.3–NA) for sorafenib. Of the 257 patients on sorafenib, 155 (60.3%) had started next-line tivozanib at the time of the analysis. Conclusions: There was no significant difference in OS between the two treatment arms. The high rate of utilization of second-line tivozanib in patients following PD on sorafenib may have affected the OS outcome. Clinical trial information: NCT01030783.
Results of a randomized, phase III trial of nab-paclitaxel (nab-P) and carboplatin (C) compared with cremophor-based paclitaxel (P) and carboplatin as first-line therapy in advanced non-small cell lung cancer (NSCLC).
Authors: M. A. Socinski, I. N. Bondarenko, N. A. Karaseva, A. Makhson, I. Vynnichenko, I. Okamoto, J. K. Hon, V. Hirsh, P. Bhar, J. Iglesias
Journal: Journal of Clinical Oncology (2010)

LBA7511 Background: Platinum-based doublet therapy in NSCLC, regardless of the combination used, reached a therapeutic plateau. PC produced 15-25% overall response (ORR, Kelly 2001; Sandler 2006; Schiller 2002). Albumin-bound paclitaxel, nab-P, utilizes the albumin receptor (gp60)/caveolin-1 (CAV1) pathway achieving high intratumoral paclitaxel accumulation (Desai 2006), which may have contributed to a 48% ORR observed with nab-PC in NSCLC (Stroyakovsky, 2009). This phase III trial studied the efficacy of nab-PC vs. PC in advanced NSCLC of all histologic types. Methods: First-line stage IIIB or IV NSCLC pts (ECOG 0/1) were randomized to C AUC6 q3w and either nab-P 100 mg/m 2 qw w/o premed (n = 521) or P 200 mg/m 2 q3w with premed (n = 531). Primary endpoint: ORR by independent radiologic review (IRR). Results: Baseline and histologic characteristics were well balanced. Dose intensity of paclitaxel was higher in nab-PC vs. PC (82 vs. 65 mg/m 2 /wk). nab-PC was superior to PC both by IRR (33 vs. 25%, p=0.005), a 31% improvement (1.31 response ratio [RR], 95% CI: 1.08, 1.59), and by investigator review (37 vs. 30%, p=0.008), a 26% improvement (1.26 RR, CI: 1.06, 1.50). Histologic analysis showed significantly improved ORR for nab-PC (n = 228) vs. PC (n = 221) in squamous cell carcinoma (SQC) pts (41 vs. 24%, p&lt;0.001, IRR), a 67% improvement (1.67 RR, CI: 1.26, 2.21). nab-PC was as effective as PC in nonSQC pts (ORR 26 vs. 25%). nab-PC was well tolerated, with significantly improved safety profile vs. PC despite higher paclitaxel dose delivered (1,338 vs. 1,100 mg/m 2 ). Conclusions: The primary endpoint was met, with significantly improved ORR and safety profile of nab-PC vs. PC as first-line therapy for advanced NSCLC. nab-PC was highly active in the SQC subset, which may in part be attributed to the aberrant CAV1 overexpression in SQC (Yoo 2003) and the high intratumoral accumulation of nab-P via the gp60-CAV1 pathway. [Table: see text] [Table: see text]
CABG or PCI: which is better for revascularization of coronary artery disease in chronic kidney disease?
Authors: Claudio Rigatto, Paul Komenda, Navdeep Tangri
Journal: Kidney International (2016)

Chronic kidney disease (CKD) is a potent risk factor for coronary artery disease and premature death. However, the optimal strategies for revascularization versus medical management remain unclear. Charytan et al. address this knowledge gap with a well-structured individual patient meta-analysis. We discuss the implications of their findings for patients with moderate CKD and highlight the need for randomized, controlled trials on this issue in more severe CKD.
Latent class analysis of bladder urothelial carcinoma to reveal sub-classes defined by alterations to chromatin and signal transduction networks.
Authors: Alex Fichtenholtz, Alyna Khan, Jeffrey S. Ross, Siraj Mahamed Ali, Vincent A. Miller, Philip J Stephens, Eric Neumann
Journal: Journal of Clinical Oncology (2016)

469 Background: 70,000 new cases of bladder urothelial carcinoma are diagnosed in the United States each year. Previous studies of this disease suggest two divergent pathways of carcinogenesis, with ~70% of cases being driven by alterations in signal transduction pathways (FGFR3, HRAS) and the remainder featuring alterations in cell cycle genes (TP53, RB1). Other studies focus on the high prevalence of alterations in chromatin remodeling genes (ARID1A, CREBBP, EP300) in this tumor type. The relationship between chromatin modifier alterations and the two bladder TCC sub-classes is not yet understood. Methods: Comprehensive genomic profiling (CGP) on 638 clinically confirmed cases of advanced bladder urothelial carcinoma was performed using the FoundationOne platform. The coding exons of 287 cancer-related and 47 introns of 19 genes frequently rearranged in cancer were sequenced and analyzed for base substitutions, insertions, deletions, copy number alterations and select gene fusions. The resultant alteration profiles were analyzed for their information content with an entropy-based approach and the profiles were subjected to hierarchical latent class analysis (LCA). Results: CGP of 488 male and 150 female UCs of median age 66 (min: 29, max: 87) resulted in 3241 detected alterations across 302 unique genes, for a mean of ~5.1 known or likely somatic alterations per sample. The most commonly altered genes were TP53, CDKN2A/B, ARID1A, KDM6A, and MLL2. Information was concentrated in the 33 most frequently altered genes. Multiple high level clusters were defined by combinatorial patterns of alterations in TP53, CDKN2A/B, RB1, and FGFR3. Sub-classes were defined by mutually exclusive alterations in the chromatin modifiers KDM6A, MLL2, and ARID1A. Conclusions: We present a global picture of UC sub-classes that encompasses previously identified local relationships including the mutual exclusivities between FGFR3 and TP53, RB1 and CDKN2A/B, and KDM6A and MLL2. In the context of clinically relevant genomic alterations that auger response to targeted therapies, identification of sub-classes of UC may further delineate response to therapy.
Antral gastric elastofibroma diagnosed by unroof biopsy with endoscopic submucosal dissection technique
Authors: Gabriele Curcio, Dario Ligresti, Antonino Granata, Gaia Chiarello, Ilaria Tarantino, Luca Barresi, Mario Traina
Journal: Endoscopy (2015)

Elastofibroma is a rare pseudotumoral lesion of the soft tissues that is usually located in the subscapular region. Because of this common location, the lesion is often reported as elastofibroma dorsi. It presents as a deep-seated, firm mass, often several centimeters in diameter, that does not adhere to overlying skin. Visceral involvement, including involvement of the gastrointestinal tract, has been described very rarely [1] [2] [3].
The Curious Case of the De-ICD: Negotiating the Dynamics of Autonomy and Paternalism in Complex Clinical Relationships
Authors: Daryl Pullman, Kathleen Hodgkinson
Journal: The American Journal of Bioethics (2016)

This article discusses the response of our ethics consultation service to an exceptional request by a patient to have his implantable cardioverter defibrillator (ICD) removed. Despite assurances that the device had saved his life on at least two occasions, and cautions that without it he would almost certainly suffer a potentially lethal cardiac event within 2 years, the patient would not be swayed. Although the patient was judged to be competent, our protracted consultation process lasted more than 8 months as we consulted, argued with, and otherwise cajoled him to change his mind, all to no avail. Justifying our at times aggressive paternalistic intervention helped us to reflect on the nature of autonomy and the dynamics of the legal, moral, and personal relationships in the clinical decision-making process.
First Clinical Application of Talen Engineered Universal CAR19 T Cells in B-ALL
Authors: Waseem Qasim, Persis Jal Amrolia, Sujith Samarasinghe, Sara Ghorashian, Hong Zhan, Sian Stafford, Katie Butler, Gul Ahsan, Kimberly Gilmour, Stuart Adams, Danielle Pinner, Robert Chiesa, Steve Chatters, Sue Swift, Nicholas Goulden, Karl Peggs, Adrian J Thrasher, Paul Veys, Martin Pule
Journal: Blood (2015)
Insight into rheumatological cause and effect through the use of Mendelian randomization
Authors: Philip C. Robinson, Hyon K. Choi, Ron Do, Tony R. Merriman
Journal: Nature Reviews Rheumatology (2016)

Mendelian randomization analysis makes use of random inheritance of genetic variants to limit confounding in tests for causal relationships between risk factors and disease outcomes. This Review considers the current and future applications, as well as the limitations, of Mendelian randomization in rheumatology. Establishing causality of risk factors is important to determine the pathogenetic mechanisms underlying rheumatic diseases, and can facilitate the design of interventions to improve care for affected patients. The presence of unmeasured confounders, as well as reverse causation, is a challenge to the assignment of causality in observational studies. Alleles for genetic variants are randomly inherited at meiosis. Mendelian randomization analysis uses these genetic variants to test whether a particular risk factor is causal for a disease outcome. In this Review of the Mendelian randomization technique, we discuss published results and potential applications in rheumatology, as well as the general clinical utility and limitations of the approach.
Depression in dementia of the Alzheimer type and in multi-infarct dementia
Authors: P Fischer, M Simanyi, W Danielczyk
Journal: American Journal of Psychiatry (1990)

The authors used the Hamilton Rating Scale for Depression and a rating of depressed mood to investigate the prevalence of depression in 55 patients with Alzheimer's disease, 37 patients with multi-infarct dementia, and 30 nondemented comparison subjects. The prevalence of depressed mood depended on the severity of dementia as measured by the Mini-Mental State examination and was significantly lower among patients in more severe stages of Alzheimer's disease but not among patients with severe multi-infarct dementia.
A New Simplified Prognostic Index with Age Cut-off of 70 Years for Patients with Diffuse Large B-Cell Lymphoma. A Population-Based Analysis From the Danish Lymphoma Registry, LYFO
Authors: Anne Ortved Gang, Michael Pedersen, Francesco d'Amore, Lars Møller-Pedersen, Bo Amdi Pedersen, Paw Jensen, Bjarne Bach Pedersen, Michael B. Møller, Ole Gadeberg, Steen Ingeberg, Torben mourits-Andersen, Stanislaw Pulczynski, Tobias Wirenfeldt Klausen, Peter De Nully Brown
Journal: Blood (2012)
Cardiovascular Autonomic Neuropathy, Sexual Dysfunction, and Urinary Incontinence in Women With Type 1 Diabetes
Authors: James M. Hotaling, Aruna V. Sarma, Darshan P. Patel, Barbara H. Braffett, Patricia A. Cleary, Eva Feldman, William H. Herman, Catherine L. Martin, Alan M. Jacobson, Hunter Wessells, Rodica Pop-Busui
Journal: Diabetes Care (2016)

OBJECTIVE This study evaluated associations among cardiovascular autonomic neuropathy (CAN), female sexual dysfunction (FSD), and urinary incontinence (UI) in women with type I diabetes mellitus (T1DM). RESEARCH DESIGN AND METHODS We studied 580 women with T1DM in the Diabetes Control and Complications Trial/Epidemiology of Diabetes Interventions and Complications Study (DCCT/EDIC). CAN was defined as: 1) R-R variation &amp;lt;15 with deep breathing or 2) R-R variation of 15–19.9 plus Valsalva ratio ≤1.5 or a supine-to-standing drop of 10 mmHg in diastolic blood pressure. A Sandvik Severity Index of 3–12 defined UI, and a Female Sexual Function Index (FSFI-R) score ≥22.75 defined FSD. Multivariable models estimated associations among CAN, FSD, and UI. RESULTS At EDIC year 17, FSD was observed in 41% of women and UI in 30%. No statistically significant associations were observed between measures of CAN at DCCT closeout and subsequent report of FSD or UI. At EDIC year 16/17, there was a 53% increased odds of having UI with a Valsalva ratio ≤1.5. At both EDIC year 13/14 and EDIC year 16/17, a 5-unit increase in R-R variation was associated with a 1.11 greater odds of having FSD. CONCLUSIONS In women with T1DM in the DCCT/EDIC, we found significant increased odds of FSD and UI with specific measures of CAN. In long-standing T1DM, CAN may predict development of FSD and may be a useful surrogate for generalized diabetic autonomic neuropathy.
IL-21 Enhances Anti-Leukemia Effect By Acting On Both CD3+CD56+ CIK Cells and Regulatory T Cells Derived From Umbilical Cord Blood In Vitro
Authors: Juanxia Meng, Mingfeng Zhao, Xiao Chai, Xia Xiao, Juan Mu, Qing Li, Qi Deng, Yuming Li
Journal: Blood (2013)
Recertification
Authors: Julie Wu
Journal: JAMA (2010)

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 HomeNew OnlineCurrent IssueFor Authors 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) Podcasts Clinical Reviews Editors' Summary Medical News Author Interviews More 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 journal
A phase I study of nivolumab (anti-PD-1; BMS-936558, ONO-4538) plus platinum-based doublet chemotherapy (PT-doublet) in chemotherapy-naive non-small cell lung cancer (NSCLC) patients (pts).
Authors: Naiyer A. Rizvi, Scott J. Antonia, Laura Quan Man Chow, Julie R. Brahmer, Rosalyn A. Juergens, Hossein Borghaei, Frances A. Shepherd, Scott Andrew Laurie, David E. Gerber, Jonathan Wade Goldman, Yun Shen, Christopher Harbison, Suresh Alaparthy, Allen C. Chen, Scott N. Gettinger
Journal: Journal of Clinical Oncology (2013)

8072 Background: A phase I study ofnivolumab (a PD-1 receptor blocking Ab) demonstrated durable responses and a tolerable safety profile in NSCLC pts who failed ≥1 chemotherapy regimen. We report an interim analysis of a phase I study with nivolumab + PT-doublets in chemotherapy-naive advanced NSCLC pts. Methods: Stage IIIB/IV NSCLC pts were randomized by histology ≥9 wk prior to data lock (Dec 2012) to: A) nivolumab/gemcitabine/cisplatin; B) nivolumab/pemetrexed/cisplatin; or C) nivolumab/carboplatin/paclitaxel according to a phase I dose de-escalation design to assess the toxicities and incidence of DLTs in the first 6 wk of dosing. Nivolumab doses were started at 10 mg/kg IV Q3W and given until progression. PT-doublet was given for 4 cycles at standard dosing. At a tolerable dose, cohorts were expanded up to 20 pts. Results: 43 pts were treated with nivolumab + PT-doublet: Arm A, n=12 squamous (sq); Arm B, n=15 (non-sq); and Arm C, n=16 (3 sq + 13 non-sq). No DLTs were seen across arms. Gr 3-4 regimen-related AEs were 49% across arms, and 25%, 47%, and 69% for Arms A, B, and C, respectively. Select Gr 3-4 toxicities reported included: pneumonitis, rash, nephritis, and colitis (Table). 3 pts had Gr 3 pneumonitis and were addressed with management algorithms (dose discontinuation and immune-modulating therapies). 2 pts fully resolved, however 1 resolved pt subsequently died from Aspergillus pneumonia. 1 pt died of disease progression with unresolved pneumonitis (autopsy confirmed). Total/Confirmed ORRs (RECIST 1.1) were 43/33%, 40/33%, and 31/31% in Arms A, B, and C, respectively. Conclusions: No DLTs were seen with 10 mg/kg nivolumab combined with PT-doublets; maintenance treatment is ongoing. Similar to monotherapy, select nivolumab related toxicities can be addressed with management algorithms. Safety, durability, and confirmation of responses will be updated based on a 2013 data analysis, including a 5 mg/kg nivolumab dose cohort. Clinical trial information: NCT01454102. [Table: see text]
Liquid Biopsy As a Tool for Monitoring the Genotype of Diffuse Large B-Cell Lymphoma
Authors: Silvia Rasi, Sara Monti, Manuela Zanni, Carmela Ciardullo, Fary Diop, Lavinia Martuscelli, Elisa Spaccarotella, Valeria Spina, Alessio Bruscaggin, Simone Favini, Clara Deambrogi, Antonio Ramponi, Gianluca Gaidano, Davide Rossi
Journal: Blood (2015)
Massive Life-Threatening Hemorrhages Due to Toxic Oral Intake of 3750 Mg Dabigatran Etexilate As a Suicide Attempt and the Clinical Management
Authors: Gursel Gunes, Umit Yavuz Malkan, Salih Aksu, Ibrahim Celalettin Haznedaroglu, Yahya Buyukasik, Nilgun Sayinalp, Osman Ilhami Ozcebe, Hakan Goker, Haluk Demiroglu
Journal: Blood (2014)
New Strategies in Esophageal Carcinoma: Translational Insights from Signaling Pathways and Immune Checkpoints
Authors: Victoria E. Wang, Jennifer R. Grandis, Andrew H. Ko
Journal: Clinical Cancer Research (2016)

Esophageal cancer remains a highly lethal malignancy in which relatively modest therapeutic advances have been made over the past several decades. Cytotoxic therapy remains the mainstay of treatment for both advanced esophageal adenocarcinoma and squamous cell carcinoma (SCC), with incremental benefit conferred by antibodies targeting HER2 and VEGFR in selected patients. However, intrinsic or acquired resistance in this disease almost invariably occurs and remains a major challenge. Moreover, although large-scale exome and whole-genome sequencing efforts have identified a variety of somatic mutations and copy number variations, particularly amplifications, in esophageal cancer, the ability to translate these findings successfully into actionable therapeutic approaches has been elusive. More recently, immunotherapeutic strategies, most notably immune checkpoint inhibitors, have demonstrated benefit to a subset of patients with both esophageal adenocarcinoma and SCC and represent an area of active clinical investigation. In this article, we discuss some of the insights derived from past trials of esophageal cancer, highlight ongoing research efforts in this arena, and emphasize the need to refine our approach to treating patients based on distinct anatomic, histologic, and molecular features. Clin Cancer Res; 22(17); 4283-90. ©2016 AACR.
Symposium: 비알콜성 지방간 및 지방간염 : 비알코올성 지방간질환의 치료
Authors: 박상훈 ( Sang Hoon Park )
Journal: Clinical and Molecular Hepatology (2010)

Recently, nonalcoholic fatty liver disease (NAFLD) is highly prevalent even in Korea, which has the potential to progress to cryptogenic cirrhosis and hepatocellular carcinoma. It is not only regarded as a hepatic component of the metabolic syndrome but also as an independent risk factor and a marker for increase in cardiovascular disease. Weight loss via lifestyle modification remains the most common and fundamental therapy advocated for reducing hepatic lipid in NAFLD. There is increasing evidence that exercise or physical activity beneficially modulates liver fat independent of weight loss. Although reduced total calorie intake potentially plays a role in the treatment of NAFLD, dietary macronutrient composition may also play a role. Low-carbohydrate and low-fructose diets are of particular benefit to reduce steatosis and improve biochemical tests. Polyunsaturated fatty acid and monounsaturated fatty acid may play a protective role against increase liver fat. Limitation of Saturated fat and trans-fatty acids intake is very recommendable. Even weight loss and physical activity continued to be the cornerstone of therapy in NAFLD, but reaching a long-term lifestyle modification is not free from difficulties. Behavior therapy may give patients the practical tools to achieve their eating and physical activity goals and incorporate and maintain them into lifestyle for long time. Some insulin-sensitizing drug may be a more effective means in the treatment of NAFLD. Vitamin E and statin have demonstrated promising initial results in improving liver enzymes or features of liver histology. However, weight loss medication is not recommended which have shown varying degrees of side effects for the treatment of NAFLD at present.