tbuckley/cabot-search huggingface dataset:
Should Transcatheter Aortic Valve Replacement Be the Procedure of Choice for Intermediate-Risk Patients With Severe Aortic Stenosis?
Authors: Paul N. Fiorilli, Jay Giri
Journal: Circulation (2018)

ranscatheter aortic valve replacement (TAVR) is considered a reasonable alternative to surgical aortic valve replacement (SAVR) in intermediate-risk patients with severe aortic stenosis (AS) as noted in the 2017 American Heart Association/American College of Cardiology focused update to the guidelines on valvular heart disease 1 (Class IIa; Level of Evidence B-R).This recommendation is based on substantial randomized evidence from the PARTNER II trial (Placement of Aortic Transcatheter Valve) and SURTAVI trial (Surgical Replacement and Transcatheter Aortic Valve Implantation). 2,3Although high-quality randomized controlled data exist to guide decision making, the extent to which TAVR and SAVR are used in a real-world, intermediate-risk population is not well defined.In this issue of Circulation, Werner et al 4 aim to shed light on the real-world use of TAVR and SAVR in intermediate-risk patients and to describe the outcomes of patients undergoing each approach.The authors analyzed data from the prospective, all-comers German Aortic Valve Registry (GARY) on 7613 patients deemed to be at intermediate surgical risk on the basis of the Society of Thoracic Surgeon's (STS) risk score undergoing either TAVR or SAVR at 92 sites in Germany between 2012 and 2014.In this national observational study, the average STS score was 5.6±1.1 for the TAVR group versus 5.2±1.0 for the SAVR group.Although this difference was statistically significant because of the large number of patients examined (P<0.001), the clinical significance of a 0.4% average difference in STS score is negligible.These STS scores closely mirror those of patients randomized in the PARTNER II trial, where the average STS score was 5.8%.Superficially, then, it would appear that the present analysis serves as a fair real-world confirmation of the results of this pivotal randomized trial.However, a closer look at the patients enrolled and their specific clinical circumstances casts some doubt on this assumption.First, patients were enrolled from the years 2012 to 2014, a time period before any prospective randomized data were available on the safety and efficacy of TAVR in an intermediate-risk population.It is likely that the extensive use of TAVR in this population (85% of the 7613 patients studied received TAVR) represented "risk creep" that has been seen in other TAVR analyses, 5 a phenomenon in which real-world populations treated with novel technologies are a bit healthier than those enrolled in pivotal trials.Indeed, a remarkable 25 of the 92 sites in the study used exclusively TAVR to treat isolated intermediate-risk AS during the study period.The primary presented analysis does not properly account for these treatment patterns or for the potential interaction of site volumes of TAVR/SAVR on outcomes.The authors attempted to address this through sensitivity analyses excluding sites that performed exclusively TAVR with additional adjustment for
Abstract 16761: Long Non-coding RNA Meg3 Controls Endothelial Cell Function: Implications for Endothelial Aging and Senescence <i>(Best of Basic Science Abstract)</i>
Authors: Reinier Boon, Patrick Hofmann, Katharina Michalik, Andrea Knau, Yuliya Ponomareva, Andreas Zeiher, Shizuka Uchida, Stefanie Dimmeler
Journal: Circulation (2015)

The majority of transcribed RNA does not encode proteins, but may function as regulatory RNA. Long non-coding RNAs (lncRNAs) have been described to play an important role in many biological processes, including epigenetic regulation of gene expression. To determine the expression and functional role of lncRNAs in endothelial cells, we performed RNA deep sequencing of human umbilical venous endothelial cells (ECs). Among the highest expressed lncRNAs, we identified Meg3 (35.3±0.6 RPKM), which was increased in replicative senescent HUVECs in vitro (passage 16/17 vs 2/3, 2.9±0.99-fold). Interestingly, Meg3 is induced in the intima of aged mice and correlates with age in human hearts (p=0.016). In HUVECs, Meg3 localizes to the nucleus and is also induced by hypoxia (4.08±0.78-fold, p&lt;0.05). Silencing of Meg3 using LNA-GapmeRs induced angiogenic sprouting and proliferation of endothelial cells in vitro (1.4±0.14-fold, P&lt;0.05) and repressed SA-β-galactosidase activity. Conversely, lentiviral overexpression of Meg3 inhibited sprouting angiogenesis and cell cycle progression, although splicing isoforms of Meg3 show differential effects. Mechanistically, RNA immunoprecipitation showed that Meg3 associates specifically to H3K27me3, a silencing chromatin mark, and interacts with EZH2, a histone methyl transferase. Silencing of Meg3 in HUVECs represses, and overexpression of Meg3 induces, global gene expression, as measured by exon array analysis. As Meg3 was described to recruit Jarid2 to chromatin, we determined whether Meg3 requires Jarid2. The Meg3 loss-of-function induced repression of proliferation was normalized after silencing Jarid2, indicating that Meg3 effects are at least partly Jarid2-dependent. Finally, silencing of Meg3 in aged mice in vivo using gapmeRs in combination with hind limb ischemia significantly repressed Meg3 levels in the hindlimb and induced recovery of perfusion compared to control mice. Capillary and arteriole density was also markedly induced after silencing Meg3. These results demonstrate that silencing Meg3 may be a potential strategy to reduce endothelial senescence or increase regenerative angiogenesis.
Boss who made £7.9m from selling fake cancer cure is jailed for 15 months
Authors: Clare Dyer
Journal: BMJ (2018)

The founder of a company selling a fake cancer cure has been jailed for 15 months after pleading guilty to money laundering and to manufacturing, selling, and supplying an unlicensed medicine.

David Noakes, who has no medical qualifications, made and distributed GcMAF (Globulin component Macrophage Activating Factor) worldwide from the UK, Southwark Crown Court was told. It was marketed as a cure for cancer, HIV, multiple sclerosis, and autism, although Noakes told the court that he no longer claimed it was a cancer cure.

His Guernsey based company, Immuno Biotech, …
Corrigendum to biocompatible bacteria-derived vesicles show inherent antimicrobial activity [Journal of controlled release, volume 290, page 46–55 (2018), page 46–55]
Authors: Eilien Schulz, Adriely Goes, Ronald Garcia, Fabian Panter, Marcus Koch, Rolf Müller, Kathrin Fuhrmann, Gregor Fuhrmann
Journal: Journal of Controlled Release (2018)
Association between asthma, rhinitis, and conjunctivitis multimorbidities with molecular IgE sensitization in adults
Authors: Valérie Siroux, Anne Boudier, Rachel Nadif, Christian Lupinek, Rudolph Valenta, Jean Bousquet
Journal: Allergy (2018)

Please note: The publisher is not responsible for the content or functionality of any supporting information supplied by the authors. Any queries (other than missing content) should be directed to the corresponding author for the article.
Abstract 14589: Mechanisms for Persistent Atrial Fibrillation - Comparing Multiple Mapping Methods at Sites of Termination: The International COMPARE-AF Registry
Authors: Tina Baykaner, Junaid Zaman, Mahmood AlHusseini, David Vidmar, Gabriela Meckler, Fatemah Shenasa, Christopher Kowalewski, Albert J Rogers, Miguel Rodrigo, David E Krummen, Nicholas S Peters, Paul J Wang, Johannes Brachmann, John M Miller, William H Sauer, Wouter J Rappel, Sanjiv M Narayan
Journal: Circulation (2017)

Introduction: Mechanisms for persistent AF are unclear. On the basis that sites where ablation terminates persistent AF may have mechanistic relevance, we performed the first systematic mapping of ...
Cyclosporine-Induced Gingival Hypertrophy
Authors: Sheetanshu Kumar, Ankur Guliani, Keshavamurthy Vinay
Journal: JAMA Dermatology (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 Dermatology 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 Dermatology journal
<i>In vivo</i> Imaging-Guided Nanoplatform for Tumor Targeting Delivery and Combined Chemo-, Gene- and Photothermal Therapy
Authors: Cheng Li, Xiao-Quan Yang, Ming-Zhen Zhang, Yuan-Yang Song, Kai Cheng, Jie An, Xiao-Shuai Zhang, Yang Xuan, Bo Liu, Yuan-Di Zhao
Journal: Theranostics (2018)

Currently, a large number of anti-tumor drug delivery systems have been widely used in cancer therapy.However, due to the molecular complexity and multidrug resistance of tumors, monotherapies remain suboptimal.Thus, this study aimed to develop a multifunctional theranostic nanoplatform for effective cancer therapy.Methods: Folic acid-modified silver sulfide@mesoporous silica core-shell nanoparticle was first modified with desthiobiotin (db) on the surface, then doxorubicin (DOX) was loaded into pore.Avidin was employed as "gatekeeper" to prevent leakage of DOX via desthiobiotin-avidin interaction.Db-modified survivin antisense oligonucleotide (db-DNA) which could inhibit survivin expression was then grafted on avidin at the outer layer of nanoparticle.DOX release and db-DNA dissociation were simultaneously triggered by overexpressing biotin in cancer cells, then combining PTT from Ag2S QD to inhibit tumor growth.Results: This nanoprobe had satisfactory stability and photothermal conversion efficiency up to 33.86% which was suitable for PTT.Due to the good targeting ability and fluorescent anti-bleaching, its signal still existed at the tumor site after tail vein injection of probe into HeLa tumor-bearing nude mice for 48 h.In vitro and in vivo antitumor experiments both demonstrated that drug, gene and photothermal synergistic therapy significantly enhanced antitumor efficacy with minimal systemic toxicity. Conclusion:Our findings demonstrate that this novel nanoplatform for targeted image-guided treatment of tumor and tactfully integrated chemotherapy, photothermal therapy (PTT) and gene therapy might provide an insight for cancer theranostics.
Effectiveness of Prophylactic Intraperitoneal Mesh Implantation for Prevention of Incisional Hernia in Patients Undergoing Open Abdominal Surgery
Authors: Andreas Kohler, Joel L. Lavanchy, Ursina Lenoir, Anita Kurmann, Daniel Candinas, Guido Beldi
Journal: JAMA Surgery (2018)

<h3>Importance</h3> Incisional hernia is a frequent complication after open abdominal surgery. Prophylactic mesh implantation in the onlay or sublay position requires dissection of the abdominal wall, potentially leading to wound-associated complications. <h3>Objective</h3> To compare the incidence of incisional hernia among patients after prophylactic intraperitoneal mesh implantation with that among patients after standard abdominal closure. <h3>Design, Setting, and Participants</h3> An open-label randomized clinical trial was performed in 169 patients undergoing elective open abdominal surgery from January 1, 2011, to February 29, 2014. Follow-up examinations were performed 1 year and 3 years after surgery. The study was conducted at Bern University Hospital, Bern, Switzerland, a referral center that offers the whole spectrum of abdominal surgical interventions. Patients with 2 or more of the following risk factors were included: overweight or obesity, diagnosis of neoplastic disease, male sex, or history of previous laparotomy. Patients were randomly assigned to prophylactic intraperitoneal mesh implantation or standard abdominal closure. Data were analyzed in August 2017. <h3>Interventions</h3> Intraperitoneal implantation of a polypropylene-polyvinylidene fluoride mesh with circumferential fixation. <h3>Main Outcomes and Measures</h3> The primary end point was the incidence of incisional hernia 3 years after surgery. Secondary end points included mesh-related complications. <h3>Results</h3> After the exclusion of 19 patients, 150 patients (81 in the control group and 69 in the mesh group; mean [SD] age, 64.2 [11.1] years; 102 [68.0%] male) were studied. The cumulative incidence of incisional hernia was significantly lower in the mesh group compared with the control group (5 of 69 [7.2%] vs 15 of 81 [18.5%], log-rank test<i>P</i> = .03). Abdominal pain was observed in significantly more patients in the mesh group compared with the control group at 6 weeks (34 of 52 [65%] vs 26 of 59 [44%],<i>P</i> = .04) but not at 12 and 36 months postoperatively. No difference in surgical site infections was observed, but time to complete wound healing of surgical site infection was significantly longer in patients with mesh implantation (median [interquartile range], 8 [6-24] weeks compared with 5 [1-9] weeks;<i>P</i> = .03). Trunk extension was significantly decreased after mesh implantation compared with the control group (mean [SD], 1.73 [0.97] cm vs 2.40 [1.23] cm,<i>P</i> = .009). <h3>Conclusions and Relevance</h3> In patients at elevated risk for incisional hernia, prophylactic intraperitoneal mesh implantation reduces the incidence of hernia formation but with increased early postoperative pain and prolonged wound healing of surgical site infection. <h3>Trial Registration</h3> ClinicalTrials.gov Identifier:NCT01203553
Visualization of asymptomatic atherosclerotic disease for optimum cardiovascular prevention (VIPVIZA): a pragmatic, open-label, randomised controlled trial
Authors: Ulf Näslund, Nawi Ng, Anna Lundgren, Eva Fhärm, Christer Grönlund, Helene Johansson, Bernt Lindahl, Bertil Lindahl, Kristina Lindvall, Stefan K Nilsson, Maria Nordin, Steven Nordin, Emma Nyman, Joacim Rocklöv, Davide Vanoli, Lars Weinehall, Patrik Wennberg, Per Wester, Margareta Norberg
Journal: The Lancet (2018)
A systematic review and combined analysis of phase III trials to evaluate the safety of adjuvant sunitinib in patients with high risk renal cell carcinoma after nephrectomy.
Authors: Miguel Quirch, Kyaw Zin Thein, Somedeb Ball, Nimesh Adhikari, Catherine Jones, Nicholas C. D'Cunha, Sanjay Awasthi, Lukman Aderoju Tijani, Fred L. Hardwicke
Journal: Journal of Clinical Oncology (2018)

214 Background: Sunitinib, an oral vascular endothelial growth factor receptor (VEGFR) tyrosine kinase inhibitor, has been approved in adjuvant treatment of high risk renal cell carcinoma (RCC) after nephrectomy despite distinct results among studies, along with notable safety concerns. We undertook a systematic review and meta-analysis of randomized controlled trials (RCT) to determine the risk of grade 3 and 4 adverse events in patients treated with adjuvant sunitinib. Methods: MEDLINE, EMBASE databases and meeting abstracts from inception through June 2018 were queried. Phase 3 RCTs which utilized adjuvant sunitinib in high risk RCC after nephrectomy were included. Mantel-Haenszel (MH) method was used to calculate the estimated pooled risk ratio (RR) with 95% confidence interval (CI). Random effects model was applied. Results: Two phase III RCTs with a total of 1866 patients were eligible. Studies utilized sunitinib versus placebo. The randomization ratio was 1:1 in both ASSURE and S-TRAC studies. The RR of high-grade adverse effects were as follows: hypertension, 4.26 (95% CI: 2.89 – 6.26, p &lt; 0.001); fatigue, 5.40 (95% CI: 3.49 – 8.34; p &lt; 0.001); rash/desquamation, 5.00 (95% CI: 1.59 – 15.68; p = 0.006); hand foot syndrome, 18.68 (95% CI: 5.98 – 58.28, p &lt; 0.001); asthenia, 6.57 (95% CI: 1.005 – 43.04; p = 0.049); diarrhea, 18.08 (95% CI: 6.63 – 49.32; p &lt; 0.001); dyspepsia, 12.68 (95% CI: 2.40 – 66.80, p = 0.003); stomatitis, 29.15 (95% CI: 5.73 – 148.18; p &lt; 0.001); nausea, 19.63 (95% CI: 3.81 – 100.97; p &lt; 0.001); and vomiting, 8.21 (95% CI: 2.21 – 30.51; p = 0.002). Conclusions: The rate of high-grade hypertension, fatigue, asthenia, dermatological toxicities, including hand foot syndrome, and gastrointestinal toxicities were extremely high in patients treated with adjuvant sunitinib, compared to placebo arm. Fatigue, hand foot syndrome and gastrointestinal toxicities significantly contribute to patients’ quality of life and providing good supportive care is warranted.
Development of an integrated palliative and supportive care service within an academic cancer center.
Authors: Sarah Loschiavo, Trena Stoute, Karen Hook
Journal: Journal of Clinical Oncology (2018)

99 Background: Timely incorporation of palliative services with chemotherapy treatment has become a new standard of care for oncology patients based on evidence-driven national clinical practice guidelines. However, best practices for service integration are not known, particularly for small academic centers. In our 224 bed university hospital, we hypothesized that advertisement, responsiveness to needs and service integration would result in increased utilization of palliative and supportive care. We report the process of developing our Integrated Model of Care. Methods: The program began with a 1.0 FTE APRN boarded as a FNP and certified as an advanced hospice and palliative nurse. The goal was to identify opportunities for her integration within the outpatient cancer center. A needs-assessment survey was sent to medical oncology faculty with the following items: proposed change in service name, care areas of greatest need, limitations to providing palliative care, additional growth opportunities. The Interdisciplinary Supportive Care Team was created utilizing existing staff. One year of billed consults were reviewed. The APRN attended tumor boards, team meetings, biweekly Interdisciplinary Team Meetings, communicated directly with the Inpatient Hem/Onc Team and provided educational sessions. Results: Needs assessment survey and service name change proposal sent to 14 oncology providers: 50% completed survey; seven responded YES to name change; zero providers responded NO. Of the 489 consults billed within the 1st year of service, 249 were inpatient and 240 outpatients. 168 individual patients were referred; &gt; 72 patients were referred to palliative/hospice services; &gt; 82 patients died. One year satisfaction survey; 17 respondents; 88.23% were satisficed and 100% would consult again. Conclusions: Medical oncology faculty at our institution responded favorably to the development of a designated “Oncology Supportive Care Service” evidenced by increased consultation and utilization of services. Optimizing clinical infrastructure, processes, education and research has led to the success of this integrated care model, lending to recruitment of additional allied health professionals and ongoing program growth.
Lifestyle medicine lays the groundwork for patient care and empowerment
Authors: Denise Lin
Journal: BMJ (2018)

The paradigm shift to lifestyle modification for treatment and prevention is quintessential.1 I strongly advocate public health teaching and implementing lifestyle medicine into curriculums because lifestyle behaviours inevitably shape future communities.

In this age of mental health crisis and stressful lifestyles, we should devote time and effort towards introducing change to improve people’s wellbeing. Advising patients to …
After Grenfell: <i>The BMJ</i> ’s Christmas 2018 appeal
Authors: Alison Shepherd
Journal: BMJ (2018)

Olivier Papegnies

Doctors of the World is a global charity that brings healthcare to the most vulnerable people, including in the UK. In June 2017 the charity’s volunteer doctors responded to a call to attend the site of the Grenfell Tower blaze, …
England has failed to close gap with similar countries in cancer outcomes, analysis finds
Authors: Nigel Hawkes
Journal: BMJ (2018)

The gap in cancer outcomes between England and similar countries has not narrowed despite 20 years of well intended effort, says a new report from the Health Foundation.1

Although England’s outcomes have improved, other countries have improved as fast and have maintained their lead. “England is towards the bottom of the table, and not closing the gap,” said Rebecca Fisher, a GP and coauthor of the report.

Mike Richards, former national cancer director and the report’s lead author, said that thousands of deaths could be avoided every year if England matched the outcomes achieved by the best in Europe. “This is the equivalent of a jumbo jet of people falling from the sky every two weeks.”

The comparisons are stark. A person given a diagnosis of colon cancer in Australia, for example, has a 71% chance of survival after five years, while a British patient with the same disease has only a 60% …
PRL-3 Promotes Ubiquitination and Degradation of AURKA and Colorectal Cancer Progression via Dephosphorylation of FZR1
Authors: Cheng Zhang, Like Qu, Shenyi Lian, Lin Meng, Li Min, Jiafei Liu, Qian Song, Lin Shen, Chengchao Shou
Journal: Cancer Research (2018)

The oncogenic phosphatase PRL-3 is highly expressed in metastatic colorectal cancer but not in nonmetastatic colorectal cancer or noncolorectal cancer metastatic cancers. Although the proinvasive capacity of PRL-3 has been validated in multiple types of cancer, its impact on colorectal cancer progression and the underlying mechanisms remain poorly understood. Here, we report that overexpressed PRL-3 stimulates G2-M arrest, chromosomal instability (CIN), self-renewal, and growth of colorectal cancer cells in xenograft models, while colorectal cancer cell proliferation is decreased. PRL-3-induced G2-M arrest was associated with decreased expression of Aurora kinase A (AURKA). PRL-3-promoted slow proliferation, CIN, self-renewal, and growth in xenografts were counteracted by ectopic expression of AURKA. Conversely, knockdown of PRL-3 resulted in low proliferation, S-phase arrest, impaired self-renewal, increased apoptosis, and diminished xenograft growth independently of AURKA. Analysis of colorectal cancer specimens showed that expression of PRL-3 was associated with high status of CIN and poor prognosis, which were antagonized by expression of AURKA. PRL-3 enhanced AURKA ubiquitination and degradation in a phosphatase-dependent fashion. PRL-3 interacted with AURKA and FZR1, a regulatory component of the APC/CFZR1 complex. Destabilization of AURKA by PRL-3 required PRL-3-mediated dephosphorylation of FZR1 and assembly of the APC/CFZR1 complex. Our study suggests that PRL-3-regulated colorectal cancer progression is collectively determined by distinct malignant phenotypes and further reveals PRL-3 as an essential regulator of APC/CFZR1 in controlling the stability of AURKA. SIGNIFICANCE: Dephosphorylation of FZR1 by PRL-3 facilitates the activity of APC/CFZR1 by destabilizing AURKA, thus influencing aggressive characteristics and overall progression of colorectal cancer.
Ravulizumab (ALXN1210) vs eculizumab in adult patients with PNH naive to complement inhibitors: the 301 study
Authors: Jong Wook Lee, Flore Sicre de Fontbrune, Lily Wong Lee Lee, Viviani Pessoa, Sandra Gualandro, Wolfgang Füreder, Vadim Ptushkin, Scott T. Rottinghaus, Lori Volles, Lori Shafner, Rasha Aguzzi, Rajendra Pradhan, Hubert Schrezenmeier, Anita Hill
Journal: Blood (2018)