tbuckley/cabot-search huggingface dataset:
Retinopathy and RAAS Activation: Results From the Canadian Study of Longevity in Type 1 Diabetes
Authors: Julie A. Lovshin, Yuliya Lytvyn, Leif E. Lovblom, Alexandra Katz, Geneviève Boulet, Petter Bjornstad, Vesta Lai, Leslie Cham, Josephine Tse, Andrej Orszag, Hillary A. Keenan, Narinder Paul, Vera Bril, David T. Wong, Kylen D. McReelis, Michael H. Brent, Bruce A. Perkins, David Z.I. Cherney
Journal: Diabetes Care (2018)

The importance of renin-angiotensin-aldosterone system (RAAS) activation in retinopathy for long-standing diabetes is not well understood. We determined retinopathy stage and evaluated associations with other vascular complications before and after physiological RAAS activation in adults with long-standing (≥50 years duration) type 1 diabetes.Participants underwent retinal examination by digital funduscopic photography and optical coherence tomography and were classified as having nonproliferative diabetic retinopathy (NPDR), proliferative diabetic retinopathy (PDR), or no diabetic retinopathy (NDR) with or without diabetic macular edema (DME). Neuropathy was measured by clinical neuropathy examination scores, electrophysiologically, and by corneal confocal microscopy. Renal function was measured by inulin and para-aminohippurate clearance methods. Arterial stiffness was measured by applanation tonometry. Renal function, blood pressure, and arterial stiffness were measured before and after RAAS activation with angiotensin II (ANGII). Associations were determined using linear regression.Twelve (16%) of the 75 participants had NDR, 24 (32%) had NPDR, and 39 (52%) had PDR. A low overall prevalence of DME (4%) was observed. Those with PDR had worse nerve function and reduced corneal nerve density, were more likely to have macrovascular disease, and had increased arterial stiffness in response to ANGII compared with those with NPDR or NDR. Prevalence of kidney disease or renal hemodynamic function did not differ by retinopathy status.PDR was associated with neuropathy severity and cardiovascular and peripheral vascular disease. In those with PDR, RAAS activation may be linked to vascular stiffening, an effect that persists in long-standing type 1 diabetes.
Abstract 15459: Left Atrial Enlargement and Ischemic Stroke: A Systematic Review and Meta-Analysis
Authors: Pavida Pachariyanon, Smathorn Thakolwiboon, Amr Ismail, Walter R Duarte Celada, Wasawat Vutthikraivit, Sikarin Upala
Journal: Circulation (2018)

Introduction: The relationship between left atrial enlargement (LAE) and ischemic stroke is not well understood. Herein, we conducted a systematic review and meta-analysis to explore the associatio...
A mutant Herpes simplex virus, HSPV-1, for treatment of oral cancer
Authors: Christopher Griffith, Edward Shillitoe
Journal: Cancer Research (2007)

3296  Although Herpes simplex virus type-1 (HSV-1) can be used as an oncolytic virus, it can infect a wide range of cells, which opens the possibility of undesirable side-effects. To increase the specificity of the virus for oral squamous cell carcinomas we replaced the promoter of the essential gene ICP-4 with the promoter/enhancer region of the highly tissue-specific Human papillomavirus type-16 (HPV-16). The novel virus was termed HSPV-1. The specificity of the HPV-16 promoter was confirmed by using a luciferase reporter gene construct, and expression was found in 2/3 oral cancer cell lines, but not in 3/3 brain cancer cell lines. When each of these cells was infected with HSPV-1 the cells expressed ICP-4, at levels that varied from 40% to 160% of that from the wild-type virus. However, these levels did not correlate with the activity of the promoter. HSPV-1 replicated in each cell type to titers that varied from 1% to 34.4% of the wild type virus, but the level of replication did not show a correlation with either the activity of the promoter in uninfected cells, the expression level of ICP-4 in infected cells, nor the type of tumor cell. To test the possibility that the promoter of HPV-16 was responding to some function of HSV, each of the three oral cancer cell types was transfected with the luciferase reporter construct and then infected with either HSV-1 or HSPV-1. A significant increase in expression was induced in each case, but was not seen when the wild-type virus had been exposed to UV light before the infection. Expression was induced by a strain of HSV-1, d120, from which the ICP-4 gene had been deleted. Thus, induction of expression from the HPV-16 promoter was dependent on the expression of immediate-early genes of HSV-1. The specificity of an oncolytic strain of HSV-1 can therefore be regulated by use of a fragment of HPV, but the design of new mutants must take into account the effects of other functions of HSV. Supported by PHS grant DE 13214
A novel hybrid fixation (percutaneous anterior pelvic bridge with K-wire) for the treatment of traumatic pelvic ring injury: A prospective study
Authors: Guangping Huang, Leyi Cai, Xufeng Jia, Yong Ji, Yu Zhou, Xiaping Mou, Qingmao Zhu, Fayou He, Zhaoyao Zhang
Journal: International Journal of Surgery (2018)
A Comparison of High‐Dose Cytarabine During Induction Versus Consolidation Therapy in Newly Diagnosed AML
Authors: Anthony P. Schwarer, Jason Butler, Kathryn Jackson, Ashanka Beligaswatte, Louisa Martin, Glen Kennedy, Zantomio Daniela, Ian Lewis, Devendra Hiwase, Joel Wight, Simon He, Andrew Grigg, Kirk Morris, Peter Mollee, Paula Marlton
Journal: HemaSphere (2018)

The proportion of patients with acute myeloid leukemia (AML) cured is increased by administering high-dose cytarabine (HiDAC). It remains uncertain whether to administer HiDAC as induction or consolidation, and whether ≥1 cycle of HiDAC is required. Our retrospective study of 416 adult AML patients, excluding good risk cytogenetics, compared a single cycle of HiDAC-based therapy followed by 2 cycles of standard-dose cytarabine (SDAC) (HiDAC induction cohort) with SDAC-based chemotherapy followed by 2 cycles of HiDAC-based chemotherapy (HiDAC consolidation cohort). Complete remission (CR) rate was greater in the HiDAC induction cohort (90% vs 78%, P < 0.01) which did not lead to an improved overall survival (48% vs 43%, P = 0.18) or disease-free survival (DFS) (39% vs 45%, P = 0.95). We noted that, after censoring for allogeneic hematopoetic stem cell transplant (alloHSCT) in CR1, the cumulative incidence of relapse was lower in the HiDAC consolidation cohort in patients with intermediate risk cytogenetics (68% vs 44%, P = 0.01), which lead to a greater DFS (30% vs 47%, P = 0.095). In the patients with adverse risk cytogenetics, the RR was numerically greater in the HiDAC consolidation cohort (52% vs 80%, P = 0.60) which lead to a lower DFS (27% vs 4%, P = 0.11). Our data show that, although the HiDAC induction cohort (1 cycle of HiDAC) achieved a greater CR rate, there were no overall survival differences between the 2 cohorts, and that the HiDAC consolidation cohort (2 cycles of HiDAC) had a lower RR and greater DFS in those patients with intermediate risk cytogenetics who did not undergo alloHSCT in CR1.
Coding Error Resulting in Change in Secondary Outcome Scores in Trial of Safety and Benefit of Discontinuing Statin Therapy Among Terminally Ill Patients
Authors: Jean S. Kutner, Amy P. Abernethy
Journal: JAMA Internal Medicine (2018)

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
Reduction of Cardiovascular Risk and Improved Estimated Glomerular Filtration Rate by SGLT2 Inhibitors, Including Dapagliflozin, Is Consistent Across the Class: An Analysis of the Placebo Arm of EXSCEL
Authors: Lindsay E. Clegg, Hiddo J.L. Heerspink, Robert C. Penland, Weifeng Tang, David W. Boulton, Srinivas Bachina, Robert D. Fox, Peter Fenici, Marcus Thuresson, Robert J. Mentz, Adrian F. Hernandez, Rury R. Holman
Journal: Diabetes Care (2018)

The sodium-glucose cotransporter 2 inhibitors (SGLT2i) empagliflozin and canagliflozin reduce the incidence of major adverse cardiovascular events (MACE), all-cause mortality (ACM), and renal events in cardiovascular outcomes trials, with observational real-world evidence suggesting class effect benefits that include dapagliflozin. We examined the placebo arm of the Exenatide Study of Cardiovascular Event Lowering (EXSCEL) to determine whether the effects of drop-in open-label dapagliflozin on MACE, ACM, and estimated glomerular filtration rate (eGFR) were consistent with the SGLT2i class as a whole.SGLT2i drop-in therapy occurred in 10.6% of EXSCEL participants, with 5.2% taking dapagliflozin. Propensity-matched cohorts of SGLT2i users and nonusers (n = 709 per group) were generated on the basis of their characteristics before open-label SGLT2i drop-in or at baseline for participants taking SGLT2i at enrollment and an equivalent study visit for non-SGLT2i users. Time to first adjudicated MACE and ACM was analyzed using Cox regression. eGFR slopes were compared between matched cohorts using a mixed-model repeated-measures analysis.In adjusted analyses, SGLT2i users (compared with nonusers) had a numerically lower risk of MACE (adjusted hazard ratio 0.79 [95% CI 0.49-1.28]), as did dapagliflozin users (0.55 [0.26-1.15]). SGLT2i users had a significantly lower ACM risk (0.51 [0.27-0.95]; dapagliflozin: 0.66 [0.25-1.72]). Compared with nonusers, eGFR slope was significantly better for SGLT2i users overall (+1.78 [95% CI 0.87-2.69] mL/min/1.73 m2 per year) and for dapagliflozin users (+2.28 [1.01-3.54] mL/min/1.73 m2 per year).This post hoc analysis of the placebo arm of EXSCEL supports a beneficial class effect for all SGLT2i, including dapagliflozin, for reduced ACM and less eGFR decline.
Improving Electronic Health Record Usability and Safety Requires Transparency
Authors: Raj M. Ratwani, Michael Hodgkins, David W. Bates
Journal: JAMA (2018)

This Viewpoint discusses ways in which vendors of electronic health record (EHR) systems can block the conduct and dissemination of EHR usability and safety research and calls for policies that promote the identification and communication of usability and safety issues.
Response to: “Antinuclear autoantibodies: discordance among four different assays” by Pacheco <i>et al</i>
Authors: David S Pisetsky, Diane M Spencer, Peter E Lipsky, Brad Rovin
Journal: Annals of the Rheumatic Diseases (2018)

We thank Dr Pacheco and colleagues for their comments1 on our article2 on the variation of testing for antinuclear antibodies (ANA) by indirect immunofluorescence (IIF) in the context of systemic lupus erythematosus (SLE). Along with findings described in other letters,3–8 the observations by Pacheco and colleagues on three different line immunoassays (LIA) and an ELISA indicate that, as in the case of other technologies, LIAs can show considerable discordance among different kits that are currently available. This study also shows that results by LIA can differ from those obtained by an ELISA.

Differences among ANA tests can have a variety of causes including assay conditions as well as the origin and biochemical properties of test antigens. …
A Global Public Health Victory for Tobacco Plain-Packaging Laws in Australia
Authors: Suzanne Zhou, Melanie Wakefield
Journal: JAMA Internal Medicine (2018)

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
Showing people scans of silent atherosclerosis helps them to reduce their cardiovascular risk
Authors: Susan Mayor
Journal: BMJ (2018)

Showing people ultrasound scan information enabling them to visualise their level of silent atherosclerosis is associated with reduced cardiovascular risk one year later compared with simply telling people about their risk factors, a pragmatic randomised study1 has shown.

“This trial shows the power of using personalised images of atherosclerosis as a tool to potentially prompt behaviour change and reduce the risk of cardiovascular disease,” said lead author Ulf Naslund, professor and chief physician in public health and clinical medicine at Umea University, Sweden.

The study included 3512 people aged 40, 50, or 60 years who were taking …
Emergent palliative radiotherapy: Dedicated personnel resources to improve workflow.
Authors: Susan Y. Wu, Lauren Boreta, Jason Chan, Christopher H. Chapman, Emily Yee, Steve E. Braunstein
Journal: Journal of Clinical Oncology (2018)

93 Background: Approximately half of patients undergoing radiotherapy (RT) do so with palliative intent. Urgent indications for RT may include neurologic compromise, pain, or bleeding. While some practices have a dedicated palliative RT team, the majority utilize an “on-call” system with a rotating outpatient radiation oncologist. We report our experience with a dedicated nurse practitioner (NP) to assist with palliative RT workflow, with the goal of expediting patient care. Methods: 226 inpatients treated with RT to a site of metastatic disease from May 2012 to May 2018 were included. Since August 2017, an NP has helped expedite emergent RT referrals. Mann-Whitney U tests were used to compare days between steps in the treatment planning process before and after integration of an NP. Results: The median age at RT was 60 years (IQR 49–69). The most common primary sites were lung (26%) and breast (12%). The most common indication for RT was symptomatic brain metastases (SBM, 33% of patients), followed by pain (27%) and spinal cord compression or cauda equina syndrome (SCC) (21%). The median time from referral (defined as initial contact by the primary team) to consultation was one day (IQR 0-2), and from referral to RT was four days (IQR 2-6). Median time from referral to RT was shorter for SCC (two days, IQR 1-4.5) and SBM (three days, IQR 1–6), than pain (five days, IQR 2–8) (p = 0.001 and p = 0.015, respectively). 68% of patients with SCC (32/47) and 35% of patients with SBM (26/74) started RT within one day of consultation. With an NP, patients were more likely to undergo simulation (sim) the same day as consultation (74% vs. 58%, p = 0.03). Same day sim was more common in patients with neurologic deficits (SCC+SBM) than those without (87% vs. 62%, p = 0.02). In those with neurologic deficits, time from consultation to sim decreased from 0.85 to 0.23 days (p = 0.04) and time from sim to RT decreased from 2.7 to 1.8 days (approaching significance, p = 0.06). In patients treated for pain, time from consultation to RT was reduced from 6.3 to 2.1 days (p = 0.02). Conclusions: For practices without a dedicated palliative RT team, involvement of an NP can improve workflow and expedite urgent RT. Further research is needed to rigorously explore quality improvement in the delivery of palliative RT.
Dual-Tracer PET/CT Differentiates 2 Types of Primary Cancers and Metastases in a Patient With Crossed Fused Renal Ectopia
Authors: Chi-lai Ho, Sirong Chen, Yim Lung Leung, Kam Chau Cheng, Yuet Hung Wong
Journal: Clinical Nuclear Medicine (2018)

A patient was found incidentally on dual-tracer (C-acetate [ACT] and F-FDG [FDG]) PET/CT for having crossed fused renal ectopia and 2 types of malignant tumors, colonic carcinoma and renal cell carcinoma (RCC), each having its own characteristic tracer avidity. Multiple liver metastases were also mutually exclusive, with a purely ACT-avid group of metastatic lesions from RCC and another FDG-avid group from colonic carcinoma. Bone and lung metastases, however, could not be readily distinguishable in terms of primary origins. Crossed fused renal ectopia is a rare anomaly, even rarer to have RCC coexisting with a second primary malignancy.
BPI-9016M, a c-Met inhibitor, suppresses tumor cell growth, migration and invasion of lung adenocarcinoma via miR203-DKK1
Authors: Panpan Zhang, Shaolei Li, Chao Lv, Jiahui Si, Ying Xiong, Lieming Ding, Yuanyuan Ma, Yue Yang
Journal: Theranostics (2018)

Activation of c-Met plays a critical role in tumorigenesis, migration and invasion in lung cancer.Here, we explored the therapeutic efficacy of a novel small-molecule c-Met inhibitor (BPI-9016M) in lung adenocarcinoma and investigated the underlying molecular mechanisms.Method: BPI-9016M, a c-Met tyrosine kinase receptor inhibitor, was used to treat patient-derived xenografts (PDX) from lung adenocarcinoma in NOD/SCID mice.Immunohistochemistry and Western blot analysis were used to determine the expression of c-Met and its downstream signaling molecules.CCK8, wound healing, and trans-well assays were used to analyze cell proliferation, spreading, migration and invasion.RNA sequencing and quantitative real-time PCR (qPCR) was used to screen and validate the expression of downstream genes in lung adenocarcinoma cells treated with BPI-9016M.Luciferase reporter assay was used to detect the interaction between miRNA and the targeted gene.Results: BPI-9016M significantly suppressed growth in three out of four lung adenocarcinoma PDX models, particularly in the tumors with high expression of c-Met.In lung adenocarcinoma cell lines, BPI-9016M treatment resulted in increased miR203, which reduced migration and invasion and also repressed Dickkopf-related protein 1 (DKK1) expression.Forced overexpression of DKK1 or down-regulation of miR203 reversed the inhibitory effect of BPI-9016M on migration and invasion.C-Met was verified to positively and negatively associate with DKK1 and miR203, respectively.High expression of c-Met/DKK1 or low expression of miR203 related to poor outcome of lung adenocarcinoma patients.Furthermore, we observed significantly enhanced tumor cell growth inhibition upon combining BPI-9016M treatment with miR203 mimics or DKK1 siRNA.Conclusion: Our data indicated that BPI-9016M is an effective agent against lung adenocarcinoma, particularly in tumors with c-Met activation, and likely functions through upregulation of miR203 leading to reduced DKK1 expression.
New guidance for mental health trusts aims to improve learning from patients’ deaths
Authors: Susan Mayor
Journal: BMJ (2018)

The Royal College of Psychiatrists has published new national guidance1 for NHS mental health trusts to help organisations learn more from patient deaths and improve their services.

“Around 2.5 million people are in contact with secondary mental health, learning disabilities, and autism services each year and the deaths of many patients will be unconnected to the care they received. But it is crucial that ways of improving services are learnt from patients’ deaths,” said Adrian James, registrar of the Royal College of Psychiatrists.

The guidance is built around a new care …
Association of Body Fat and Risk of Breast Cancer in Postmenopausal Women With Normal Body Mass Index
Authors: Neil M. Iyengar, Rhonda Arthur, JoAnn E. Manson, Rowan T. Chlebowski, Candyce H. Kroenke, Lindsay Peterson, Ting-Yuan D. Cheng, Elizabeth C. Feliciano, Dorothy Lane, Juhua Luo, Rami Nassir, Kathy Pan, Sylvia Wassertheil-Smoller, Victor Kamensky, Thomas E. Rohan, Andrew J. Dannenberg
Journal: JAMA Oncology (2018)

Obesity is associated with an increased risk of breast cancer, including the estrogen receptor (ER)-positive subtype in postmenopausal women. Whether excess adiposity is associated with increased risk in women with a normal body mass index (BMI; calculated as weight in kilograms divided by height in meters squared) is unknown.
AB1294 Impact of work status on health-related quality of life (HRQOL) in ra
Authors: E. Alemao, A. Boonen, Z. Guo, C. Iannaccone, M. Frits, M.E. Weinblatt, N.A. Shadick
Journal: Annals of the Rheumatic Diseases (2018)

<h3>Background</h3> Compared to the general population, RA patients (pts) are less likely to be employed and have lower HRQoL.<sup>1,2</sup> However, data on impact of work status on HRQoL in RA pts are limited. <h3>Objectives</h3> Evaluate association between work status and HRQoL in RA pts. <h3>Methods</h3> We analysed data from adult pts enrolled in a large sequential RA registry. Physicians assessed pt demographics, clinical characteristics, disease activity and laboratory parameters at baseline (BL) and then annually. Follow-up questionnaires to assess pt-reported outcomes were administered every 6 months and included HRQoL measures (12-Item Short-Form Health Survey physical and mental component summary [SF-12 PCS, MCS], EuroQoL-5 Dimension [EQ-5D]) and work status; higher score indicates better health for all 3 HRQoL measures. General linear mixed models with repeated measures were used for SF-12 analysis and finite mixture models for the EQ-5D analysis, controlling for BL covariates. <h3>Results</h3> A total of 974 RA pts with HRQoL information were included: 49.3% (n=480) 'employed for pay', 38.9% (n=379) 'employed not for pay' (retired, homemaker or student), 11.8% (n=115) 'not employed or on disability'. Pts employed for pay were younger and had lower disease activity compared with other groups (table 1). Compared with pts 'not employed or on disability', pts employed had significantly higher PCS (mean [SE] 7.17 [0.82]; p&lt;0.001), MCS (5.39 [0.80]; p&lt;0.001) and EQ-5D (0.48 [0.16]; p=0.0031) scores. Similar results were observed comparing pts 'employed not for pay' to pts 'not employed or on disability' (Table 2). <h3>Conclusions</h3> Work status and household income in RA are independently associated with HRQoL. More studies are needed to evaluate impact of work on changes in HRQoL in RA pts. <h3>References</h3> [1] Uhlig T, et al. J Rheumatol2007;34:1241–7. [2] Chorus AM, et al. Ann Rheum Dis2003;62:1178–84. <h3>Disclosure of Interest</h3> E. Alemao Shareholder of: Bristol-Myers Squibb, Employee of: Bristol-Myers Squibb, A. Boonen: None declared, Z. Guo Shareholder of: Bristol-Myers Squibb, Employee of: Bristol-Myers Squibb, C. Iannaccone: None declared, M. Frits: None declared, M. Weinblatt Grant/research support from: Amgen, Bristol-Myers Squibb, Crescendo Bioscience, Sanofi, Consultant for: AbbVie, Amgen, Bristol-Myers Squibb, Crescendo Bioscience, Lilly, Merck, Novartis, Pfizer, Roche, Samsung, N. Shadick Grant/research support from: Amgen, BRASS registry, Bristol-Myers Squibb, Mallinckrodt, Consultant for: Bristol-Myers Squibb