tbuckley/cabot-search huggingface dataset:
Frailty and Risk of Fractures in Patients With Type 2 Diabetes
Authors: Guowei Li, Jerilynn C. Prior, William D. Leslie, Lehana Thabane, Alexandra Papaioannou, Robert G. Josse, Stephanie M. Kaiser, Christopher S. Kovacs, Tassos Anastassiades, Tanveer Towheed, K. Shawn Davison, Mitchell Levine, David Goltzman, Jonathan D. Adachi
Journal: Diabetes Care (2019)

We aimed to explore whether frailty was associated with fracture risk and whether frailty could modify the propensity of type 2 diabetes toward increased risk of fractures.Data were from a prospective cohort study. Our primary outcome was time to the first incident clinical fragility fracture; secondary outcomes included time to hip fracture and to clinical spine fracture. Frailty status was measured by a Frailty Index (FI) of deficit accumulation. The Cox model incorporating an interaction term (frailty × diabetes) was used for analyses.The analysis included 3,149 (70% women) participants; 138 (60% women) had diabetes. Higher bone mineral density and FI were observed in participants with diabetes compared with control subjects. A significant relationship between the FI and the risk of incident fragility fractures was found, with a hazard ratio (HR) of 1.02 (95% CI 1.01-1.03) and 1.19 (95% CI 1.10-1.33) for per-0.01 and per-0.10 FI increase, respectively. The interaction was also statistically significant (P = 0.018). The HR for per-0.1 increase in the FI was 1.33 for participants with diabetes and 1.19 for those without diabetes if combining the estimate for the FI itself with the estimate from the interaction term. No evidence of interaction between frailty and diabetes was found for risk of hip and clinical spine fractures.Participants with type 2 diabetes were significantly frailer than individuals without diabetes. Frailty increases the risk of fragility fracture and enhances the effect of diabetes on fragility fractures. Particular attention should be paid to diabetes as a risk factor for fragility fractures in those who are frail.
Abstract 15486: Spironolactone Reduces Severity of Obstructive Sleep Apnea in Resistant Hypertension
Authors: Eric Judd, Roberto Pisoni, Tanja Dudenbostel, Suzanne Oparil, Susan M Harding, David A Calhoun
Journal: Circulation (2012)

Purpose: Plasma aldosterone levels are positively correlated with obstructive sleep apnea (OSA) severity in patients with resistant HTN but not in normotensive patients. This suggests a mechanistic...
Long-Term Update from the Open-Label Extension of the NEURO-TTR Study in Patients with Hereditary Transthyretin Amyloidosis
Authors: Thomas Brannagan, Annabel K. Wang, Teresa Coelho, Marcia Waddington Cruz, Michael J. Polydefkis, Peter J. Dyck, Violaine Plante-Bordeneuve, John L. Berk, Fabio Barroso, Giampaolo Merlini, Isabel Conceição, Steven G. Hughes, Jesse G. Kwoh, Shiangtung W. Jung, Spencer Guthrie, Michael Pollock, Merrill D. Benson, Morie A. Gertz
Journal: Blood (2018)
Use of Statins, Survival and Incidence of Thrombosis Among Older Adults with Essential Thrombocythemia: A Population-Based Study
Authors: Nikolai Podoltsev, Mengxin Zhu, Rong Wang, Amer M. Zeidan, Xiaoyi Wang, Scott F Huntington, Smith Giri, Amy J. Davidoff, Steven D. Gore, Xiaomei Ma
Journal: Blood (2018)
Adoptive T-Cell Therapy with TCL1-Specific TCR for B-Cell Lymphomas
Authors: Jinsheng Weng, Kelsey Moriarty, Yong Pan, Man Chun John MA, Rohit Mathur, Zheng Zhang, Hiroki Torikai, Sourindra N Maiti, Fuliang Chu, Xiaoyun Cheng, Swathi Karri, Deepshika Medapalli, Laurence J N Cooper, R. Eric Davis, Sattva S. Neelapu
Journal: Blood (2018)
Abstract 10647: Translational Systems Genetics, Electronic Medical Record Analysis, and Molecular Imaging Reveal That the Antidepressant Trazodone Reduces Atherosclerosis as Well as Statins: Drug Discovery by Repurposing of Proven Safe Drugs
Authors: Kipp W Johnson, Jagat Narula, Benjamin S Glicksberg, Khader Shameer, Farhan Chaudhry, Alexandre Yahi, Ben Readhead, Nayaab S Khan, Letizia Amadori, Christine Becker, Aparna A Divaraniya, Milo R Smith, Li Li, Yuliya Vengrenyuk, Benjamin McCauley, Deepak Kaji, David Stark, Koon Yan Pak, Brian Gray, Usman Baber, Nick Tatonetti, Atul J Butte, Artiom Petrov, Navneet Narula, Chiara Giannarelli, Samin K Sharma, Joel T Dudley, Annapoorna S Kini
Journal: Circulation (2018)

Introduction: Statins not infrequently fall short of target reduction in hyperlipidemia. Recently approved anti-lipid drugs are prohibitively expensive. Repurposing previously-approved drugs for ne...
Combined Aurora Kinase A (AURKA) and WEE1 Inhibition Demonstrates Synergistic Antitumor Effect in Squamous Cell Carcinoma of the Head and Neck
Authors: Jong Woo Lee, Janaki Parameswaran, Teresa Sandoval-Schaefer, Kyung Jin Eoh, Dong-hua Yang, Fang Zhu, Ranee Mehra, Roshan Sharma, Stephen G. Gaffney, Elizabeth B. Perry, Jeffrey P. Townsend, Ilya G. Serebriiskii, Erica A. Golemis, Natalia Issaeva, Wendell G. Yarbrough, Ja Seok Koo, Barbara Burtness
Journal: Clinical Cancer Research (2019)

Human papillomavirus (HPV)-negative head and neck squamous cell carcinomas (HNSCC) commonly bear disruptive mutations in TP53, resulting in treatment resistance. In these patients, direct targeting of p53 has not been successful, but synthetic lethal approaches have promise. Although Aurora A kinase (AURKA) is overexpressed and an oncogenic driver, its inhibition has only modest clinical effects in HPV-negative HNSCC. We explored a novel combination of AURKA and WEE1 inhibition to overcome intrinsic resistance to AURKA inhibition.Experimental Design: AURKA protein expression was determined by fluorescence-based automated quantitative analysis of patient specimens and correlated with survival. We evaluated treatment with the AURKA inhibitor alisertib (MLN8237) and the WEE1 inhibitor adavosertib (AZD1775), alone or in combination, using in vitro and in vivo HNSCC models.Elevated nuclear AURKA correlated with worse survival among patients with p16(-) HNSCC. Alisertib caused spindle defects, G2-M arrest and inhibitory CDK1 phosphorylation, and cytostasis in TP53 mutant HNSCC FaDu and UNC7 cells. Addition of adavosertib to alisertib instead triggered mitotic entry and mitotic catastrophe. Moreover, in FaDu and Detroit 562 xenografts, this combination demonstrated synergistic effects on tumor growth and extended overall survival compared with either vehicle or single-agent treatment.Combinatorial treatment with adavosertib and alisertib leads to synergistic antitumor effects in in vitro and in vivo HNSCC models. These findings suggest a novel rational combination, providing a promising therapeutic avenue for TP53-mutated cancers.
Abstract 18697: Utilization of Atrial Flutter Ablation and its Complications - Analysis of 38000 Procedures
Authors: Ghanshyambhai T Savani, Sadip Pant, Vipulkumar Bhalara, Ankit Chothani, Nileshkumar J Patel, Neeraj Shah, Kathan Mehta, Peeyush Grover, Vikas Singh, Naga Venkata K Pothineni, Abhishek Deshmukh, Dhaval Khalpada, Alexis Rodriguez, Apurva O Badheka, Raul D Mitrani, Hakan Paydak
Journal: Circulation (2013)

Introduction: Radiofrequency ablation (RFA) of atrial flutter (AFL) is considered as a reasonable approach due to its effectiveness, feasibility and safety. Data regarding the utilization and safety of RFA for AFL outside of selected centers of excellence and in older patients are limited. Methods: Using the Nationwide Inpatient Sample (NIS) between the years 2000-2008, we developed a coding algorithm to identify AFL patients treated with ablations. We investigated common complications like cardiac perforation and/or tamponade, pneumothorax, stroke, transient ischemic attack (TIA), vascular access complication (consisting of hemorrhage/hematoma, vascular complication requiring surgical repair, and accidental puncture), and in-hospital death described with AFL ablation and defined them by validated International Classification of Diseases (9th Edition) Clinical Modification (ICD-9-CM) diagnosis codes. Results: There were a total of 38,881 AFL ablations performed from the years 2000 to 2008. Majority of ablations were performed in patients with age &gt; 65 years, men, white race, less severe comorbidities, large bed size and teaching hospitals. The overall inhospital mortality was 15/1000. The overall complication rate was 0.3%. On multivariate analysis, apart from male gender, patient and hospital characteristics were not associated with increased complications. The length of stay and total charges were 1.5 and 2.5 times more in hospitalizations associated with complications. Conclusions: AFL ablation is safe with perforation/tamponade and vascular access complications accounting for the majority
Efficacy of Internet-Based Cognitive Behavioral Therapy for Treatment-Induced Menopausal Symptoms in Breast Cancer Survivors: Results of a Randomized Controlled Trial
Authors: Vera Atema, Marieke van Leeuwen, Jacobien M. Kieffer, Hester S.A. Oldenburg, Marc van Beurden, Miranda A. Gerritsma, Marianne A. Kuenen, Peter W. Plaisier, Alexander M.F. Lopes Cardozo, Yvonne E.A. van Riet, Gijsbert Heuff, Herman Rijna, Suzan van der Meij, Eva M. Noorda, Gert-Jan Timmers, Bart C. Vrouenraets, Matthé Bollen, Henk van der Veen, Nina Bijker, Myra S. Hunter, Neil K. Aaronson
Journal: Journal of Clinical Oncology (2019)

We evaluated the effect of Internet-based cognitive behavioral therapy (iCBT), with or without therapist support, on the perceived impact of hot flushes and night sweats (HF/NS) and overall levels of menopausal symptoms (primary outcomes), sleep quality, HF/NS frequency, sexual functioning, psychological distress, and health-related quality of life in breast cancer survivors with treatment-induced menopausal symptoms.We randomly assigned 254 breast cancer survivors to a therapist-guided or a self-managed iCBT group or to a waiting list control group. The 6-week iCBT program included psycho-education, behavior monitoring, and cognitive restructuring. Questionnaires were administered at baseline and at 10 weeks and 24 weeks postrandomization. We used mixed-effects models to compare the intervention groups with the control group over time. Significance was set at P < .01. An effect size (ES) of .20 was considered small, .50 moderate and clinically significant, and .80 large.Compared with the control group, the guided and self-managed iCBT groups reported a significant decrease in the perceived impact of HF/NS (ES, .63 and .56, respectively; both P < .001) and improvement in sleep quality (ES, .57 and .41; both P < .001). The guided group also reported significant improvement in overall levels of menopausal symptoms (ES, .33; P = .003), and NS frequency (ES, .64; P < .001). At longer-term follow-up (24 weeks), the effects remained significant, with a smaller ES for the guided group on perceived impact of HF/NS and sleep quality and for the self-managed group on overall levels of menopausal symptoms. Additional longer-term effects for both intervention groups were found for hot flush frequency.iCBT, with or without therapist support, has clinically significant, salutary effects on the perceived impact and frequency of HF/NS, overall levels of menopausal symptoms, and sleep quality.
Health visitor numbers: silk purse or sow’s ear?
Authors: Chris Tiley
Journal: BMJ (2019)

Hiam and Dorling critique the government’s new prevention plan.1 My colleagues and I have become concerned about difficulties accessing the support of health visitors.

A request under the Freedom of Information Act shows that in 2012 there were 76 full time equivalent health visitors in Cornwall, which rose to a peak of 117 in 2015, then fell by 29% to 83 in 2018. …
Diffuse Skeletal Hemangiomatosis Mimicking Metastastic Disease on 18F-FDG PET/CT
Authors: Dong Huang, Xiaohong Ou, Yunxia Ye, Wenjie Zhang
Journal: Clinical Nuclear Medicine (2019)

Diffuse skeletal hemangiomatosis is a rare vascular proliferation disorder involving multiple bones and may be confused with metastatic bone malignancy. We present a case of a 53-year-old man suffering back and proximal right femur pain underwent F-FDG PET/CT scan. Multiple hypermetabolic lesions of bone were concerning for metastatic carcinoma. Since no primary malignancy was found, open biopsy was performed and histologic examination led to a diagnosis of diffuse skeletal angiomatosis. This case highlighted the importance of including diffuse skeletal hemangiomatosis in the differential diagnosis of multiple hypermetabolic skeletal lesions on F-FDG PET/CT.
Founding Precision Therapy in 1q-Amplified Multiple Myeloma
Authors: Romanos Sklavenitis-Pistofidis, Mairead Reidy, Daisy Huynh, Karma Ziad Salem, Jihye Park, Siobhan Glavey, Xavier Leleu, David Root, Irene M. Ghobrial, Salomon Manier
Journal: Blood (2018)
Tofacitinib in Combination With Methotrexate in Patients With Rheumatoid Arthritis: Clinical Efficacy, Radiographic, and Safety Outcomes From a Twenty‐Four–Month, Phase <scp>III</scp> Study
Authors: Désirée van der Heijde, Vibeke Strand, Yoshiya Tanaka, Edward Keystone, Joel Kremer, Cristiano A. F. Zerbini, Mario H. Cardiel, Stanley Cohen, Peter Nash, Yeong‐Wook Song, Dana Tegzová, David Gruben, Gene Wallenstein, Carol A. Connell, Roy Fleischmann
Journal: Arthritis & Rheumatology (2019)

Tofacitinib is an oral JAK inhibitor for the treatment of rheumatoid arthritis (RA). The phase III, 24-month, placebo-controlled Oral Rheumatoid Arthritis (ORAL) Scan trial was undertaken to evaluate the efficacy, including inhibition of structural progression, and safety of tofacitinib in patients with active RA and an inadequate response to methotrexate (MTX). Month 24 data from the completed study are reported here.Patients were randomized 4:4:1:1 to receive tofacitinib 5 mg or 10 mg twice daily, or placebo, switched to tofacitinib 5 mg or 10 mg twice daily, with stable background MTX. Patients receiving placebo switched to tofacitinib at month 3 (nonresponders) or month 6 (remaining patients). Clinical efficacy, structural progression, and treatment-emergent adverse events were evaluated. Analyses were performed on the full analysis set with observed data or nonresponder imputation with no advancement penalty for clinical efficacy, and imputation by linear extrapolation for structural progression.Overall, 797 patients were treated; 539 (67.6%) completed 24 months of treatment. Responses according to the American College of Rheumatology criteria for 20% improvement (ACR20), ACR50, and ACR70; the proportion of patients in whom remission or low disease activity was achieved according to the 4-variable Disease Activity Score in 28 joints using the erythrocyte sedimentation rate, Clinical Disease Activity Index, or Simplified Disease Activity Index; Boolean remission; and Health Assessment Questionnaire disability index scores were maintained from month 12 to 24 and were similar between tofacitinib dosages. Limited structural damage was observed at months 12 and 24. Safety events were similar in type and frequency for both tofacitinib dosages, and were consistent with those previously reported.Our findings indicate that clinical and radiographic treatment effects are sustained in months 12-24 in patients with RA receiving tofacitinib 5 mg or 10 mg twice daily plus MTX. The safety profile is consistent with that of other tofacitinib studies.
The 2018 Farm Bill—Implications and Opportunities for Public Health
Authors: Dariush Mozaffarian, Timothy Griffin, Jerold Mande
Journal: JAMA (2019)

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 Podcasts Clinical Reviews Editors' Summary Medical News Author Interviews More 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 journal
Ixazomib, lenalidomide, and dexamethasone in patients with newly diagnosed multiple myeloma: long-term follow-up including ixazomib maintenance
Authors: Shaji K. Kumar, Jesus G. Berdeja, Ruben Niesvizky, Sagar Lonial, Jacob P. Laubach, Mehdi Hamadani, A. Keith Stewart, Parameswaran Hari, Vivek Roy, Robert Vescio, Jonathan L. Kaufman, Deborah Berg, Eileen Liao, S. Vincent Rajkumar, Paul G. Richardson
Journal: Leukemia (2019)

Triplet combinations containing a proteasome inhibitor are a standard of care in newly diagnosed multiple myeloma (NDMM). We examined the long-term efficacy and safety of the all-oral combination of weekly ixazomib plus lenalidomide-dexamethasone (IRd), followed by single-agent ixazomib maintenance in NDMM patients. Of 65 enrolled patients, 53 received ixazomib 4 mg (days 1, 8, and 15) plus lenalidomide 25 mg (days 1–21) and dexamethasone 40 mg (days 1, 8, 15, and 22) for up to twelve 28-day induction cycles. Twenty-three patients discontinued induction for stem cell transplantation (SCT). In the remaining 42 patients, overall response rate was 80%, including 63% ≥very good partial response (VGPR) and 32% complete responses. At a median follow-up of 56 months, median progression-free survival (PFS) was 35.4 months in the total population. Twenty-five patients received ixazomib maintenance; eight deepened their response (76% ≥VGPR), and median PFS was 37.2 months in this subgroup. Nine of 42 patients who did not proceed to SCT (14% of total population) had an adverse event requiring discontinuation. Ixazomib (median ≥ 96%) and lenalidomide (median 88–94%) relative dose intensities were maintained throughout treatment. Weekly IRd, followed by ixazomib maintenance, was highly active with acceptable toxicity, enabling long-term administration with no evidence of cumulative toxicities.
Abstract 15622: Evaluation of Treatment With Fimasartan and Ivabradine in Animal Myocardial Infarction Model using Cardiac Positron Emission Tomography
Authors: Hyukjin Park, Young Joon Hong, Ji Eun Kim, Min Chul Kim, Jae Yeong Cho, Hyun Ju Yoon, Kye Hun Kim, Youngkeun Ahn, Myung Ho Jeong, Jeong Gwan Cho, Jong Chun Park
Journal: Circulation (2016)

Background/Objectives: The aim of this study was to evaluate efficacy of fimasartan and ivabradine on reverse remodeling and reducing infarct size in animal myocardial infarction (MI) model, using ...
Integrated profiling the patterns of pathologic response to neoadjuvant chemoradiation and the genomic-based radiation sensitivity in rectal cancer.
Authors: Zhigang Yuan, Kamran A. Ahmed, Syeda Mahrukh Hussnain Naqvi, Michael J. Schell, Seth Felder, Julian Sanchez, Sophie Dessureault, Iman Imanirad, Richard D. Kim, Javier Torres-Roca, Sarah E. Hoffe, Jessica Frakes
Journal: Journal of Clinical Oncology (2019)

573 Background: Given the lack of biomarkers to predict a pathologic complete response (pCR) after neoadjuvant chemoradiation (NACRT) for rectal cancer, selection for non-operative management (NOM) mandates complete clinical response. We have previously developed/validated a model to assess genomic-based tumor radiosensitivity: the radiosensitivity index (RSI), which formulates a clinically actionable model to calculate genomic-adjusted radiation dose (GARD). We determined the profiles of RSI and GARD for rectal cancer and correlated these findings with the pathologic response patterns. Methods: One hundred seventeen rectal cancer patients treated from 2009 to 2018 with NACRT were assessed for the tumor regression grade (TRG) (0 = pCR; 1 = moderate response; 2 = partial response; 3 = poor response). RSI was analyzed in an independent tissue cohort of 113 resected rectal cancer samples. GARD was derived as described before, which shows a high GARD value indicated a superior therapeutic effect of radiation. Results: Median follow-up from completion of NACRT was 26 months. The primary tumor stages were 7% T2, 84% T3, and 9% T4. The majority of patients (82%) received concurrent 5-FU or Capecitabine and (83%) received RT dose of 50.4 Gy (range 45-56 Gy). Median time from end of NACRT to surgery was 61 days (range 36-105 days). The patterns of pathological response were TRG 0 (n = 24; 21%), 1 (n = 62; 53%), 2 (n = 25; 21%), and 3 (n = 6; 5%), suggesting heterogeneous sensitivity to treatment with similar tumor stage and treatment regimens. The median RSI for the tissue cohort was 0.46 (range 0.19-0.81) with 37% of the samples considered radiosensitive based on prior data. GARD values ranged from 5.17 to 41.79 (median 19.24), suggesting heterogeneous RT therapeutic effects. Conclusions: The findings from the clinical cohort were consistent with the tissue cohort showing significant heterogeneity in the individual tumor radiosensitivity and GARD-based RT therapeutic effects. With the development of GARD-based prospective trials, we anticipate more biology-based customized RT dosing which could optimize patient selection for NOM and individualize the most appropriate dose for each patient.
Immune Microenvironment Analysis of Bone Marrow By Mass Cytometry and RNA Sequencing in Multiple Myeloma Patients Treated with Daratumumab and Durvalumab
Authors: Frances Seymour, Mary H Young, Mark Tometsko, Jamie Cavenagh, Ethan G. Thompson, Elizabeth Whalen, Sam A Danziger, Alison Fitch, Brian A. Fox, Andrew Dervan, Teri Foy, Katie Newhall, John G. Gribben
Journal: Blood (2018)
Long-term correction of hemophilia B using adenoviral delivery of CRISPR/Cas9
Authors: Calvin J. Stephens, Elvin J. Lauron, Elena Kashentseva, Zhi Hong Lu, Wayne M. Yokoyama, David T. Curiel
Journal: Journal of Controlled Release (2019)

Hemophilia B (HB) is a life-threatening inherited disease caused by mutations in the FIX gene, leading to reduced protein function and abnormal blood clotting. Due to its monogenic nature, HB is one of the primary targets for gene therapy. Indeed, successful correction of HB has been shown in clinical trials using gene therapy approaches. However, application of these strategies to non-adult patients is limited due to high cell turnover as young patients develop, resulting in vector dilution and subsequent loss of therapeutic expression. Gene editing can potentially overcome this issue by permanently inserting the corrective gene. Integration allows replication of the therapeutic transgene at every cell division and can avoid issues associated with vector dilution. In this study, we explored adenovirus as a platform for corrective CRISPR/Cas9-mediated gene knock-in. We determined as a proof-of-principle that adenoviral delivery of CRISPR/Cas9 is capable of corrective gene addition, leading to long-term augmentation of FIX activity and phenotypic correction in a murine model of juvenile HB. While we found on-target error-free integration in all examined samples, some mice also contained mutations at the integration target site. Additionally, we detected adaptive immune responses against the vector and Cas9 nuclease. Overall, our findings show that the adenovirus platform is suitable for gene insertion in juveniles with inherited disease, suggesting this approach may be applicable to other diseases.