tbuckley/cabot-search huggingface dataset:
Stereotactic body radiation therapy with androgen deprivation therapy for unfavorable-risk prostate cancer.
Authors: Sagar Anil Patel, Jeffrey M. Switchenko, Chao Zhang, Brent Shane Rose, Benjamin Walker Fischer-Valuck, Ashesh B. Jani, Ronald C. Chen, Trevor Joseph Royce
Journal: Journal of Clinical Oncology (2020)

332 Background: Current ASTRO consensus guidelines do not support routine use of SBRT in higher risk PC. However, the NCCN permits selective use of SBRT with ADT for unfavorable intermediate (UIR) and high (HiR) risk PC in cases where conventional/moderately fractionated radiation therapy (EBRT) present medical or social hardship. How SBRT+ADT compares to EBRT+ADT in UIR and HiR men is unknown. Methods: Men &gt;40 years old with localized PC treated with RT and concomitant ADT for curative intent between 2004-2015 were analyzed from the National Cancer Database. Patients treated with brachytherapy or who lacked ADT or risk stratification data were excluded. A total of 558 men treated with SBRT (5 fractions, ≥7 Gy/fraction) versus 40,797 men treated with moderate or conventional EBRT (dose ≥60 Gy with ≤3 Gy/fraction) were included. Patients were stratified by UIR and HiR using NCCN criteria. Kaplan Meier and Cox proportional hazards were used to compare overall survival (OS) between RT modality, adjusting for age, race, and comorbidity index. Results: With a median follow up of 62 months, there was no difference in 5-year OS between men treated with SBRT versus EBRT regardless of risk group (UIR: 87.2% SBRT versus 87.0% EBRT, p=.40; HiR: 80.4% SBRT versus 80.8% EBRT, p=.21). On multivariable analysis, there was no difference in risk of death for men treated with SBRT compared to EBRT (UIR: adjusted HR 1.09, 95% CI 0.68-1.74, p=.72; HiR: adjusted HR 0.93, 95% CI 0.76-1.14, p=.51). Conclusions: We found no difference in survival between SBRT+ADT and standard of care EBRT+ADT for UIR or HiR PC. Randomized trials of SBRT versus EBRT, with standard concomitant ADT, in these risks groups are needed. If prospectively validated, more widespread use of SBRT for higher risk PC may be warranted, especially in an era of cost-effective care.
Contact isolation versus standard precautions to decrease acquisition of extended-spectrum β-lactamase-producing Enterobacterales in non-critical care wards: a cluster-randomised crossover trial
Authors: Friederike Maechler, Frank Schwab, Sonja Hansen, Carolina Fankhauser, Stephan Harbarth, Benedikt D Huttner, Cristina Diaz-Agero, Nieves Lopez, Rafael Canton, Patricia Ruiz-Garbajosa, Hetty Blok, Marc J Bonten, Fieke Kloosterman, Joost Schotsman, Ben S Cooper, Michael Behnke, Jennifer Golembus, Axel Kola, Petra Gastmeier
Journal: The Lancet Infectious Diseases (2020)
Dapagliflozin reduced worsening HF or CV death in HF with reduced ejection fraction
Authors: Kristen Sullivan, Harriette G.C. Van Spall
Journal: Annals of Internal Medicine (2020)

ACP Journal Club18 February 2020Dapagliflozin reduced worsening HF or CV death in HF with reduced ejection fractionKristen Sullivan, MD, Harriette G.C. Van Spall, MD, MPH, FRCPCKristen Sullivan, MDMcMaster University, Hamilton, Ontario, Canada (K.S., H.G.V.)Search for more papers by this author, Harriette G.C. Van Spall, MD, MPH, FRCPCMcMaster University, Hamilton, Ontario, Canada (K.S., H.G.V.)Search for more papers by this authorAuthor, Article, and Disclosure Informationhttps://doi.org/10.7326/ACPJ202002180-016 SectionsAboutFull TextPDF ToolsAdd to favoritesDownload CitationsTrack CitationsPermissions ShareFacebookTwitterLinkedInRedditEmail Source CitationMcMurray JJV, Solomon SD, Inzucchi SE, et al. Dapagliflozin in patients with heart failure and reduced ejection fraction. N Engl J Med. 2019;381:1995-2008. https://pubmed.ncbi.nlm.nih.gov/31535829Clinical Impact RatingsGIM/FP/GP: Cardiology: Reference1 Zelniker TA, Wiviott SD, Raz I, et al. SGLT2 inhibitors for primary and secondary prevention of cardiovascular and renal outcomes in type 2 diabetes: a systematic review and meta-analysis of cardiovascular outcome trials. Lancet. 2019;393:31-9. [PMID: 30424892] Google Scholar Author, Article, and Disclosure InformationAffiliations: McMaster University, Hamilton, Ontario, Canada (K.S., H.G.V.)Disclosures: The commentators have disclosed no conflicts of interest. The form can be viewed at www.acponline.org/authors/icmje/ConflictOfInterestForms.do?msNum=M19-3039.This article was published at Annals.org on 4 February 2020. PreviousarticleNextarticle Advertisement FiguresReferencesRelatedDetails Metrics 18 February 2020Volume 172, Issue 4Page: JC16KeywordsDrug informationDrug therapyEjection fractionEstimated glomerular filtration rateHeart failureHospitalizationsHypotensionType 1 diabetesType 2 diabetesVital statistics ePublished: 18 February 2020 Issue Published: 18 February 2020 Copyright & PermissionsCopyright © 2020 by American College of Physicians. All Rights Reserved.PDF downloadLoading ...
CASSIOPE: A real-world study assessing the use of cabozantinib for the treatment of advanced renal cell carcinoma (aRCC) after vascular endothelial growth factor (VEGF)-targeted therapy in Europe.
Authors: Michael D. Staehler, Paul Hamberg, Pierre Bigot, Cristina Suárez, Philippe Barthelemy, Jean-Christophe Eymard, Mathieu Laramas, Naila Taguieva Pioger, Marine Gross-Goupil, Michael Rink, Cristina Masini, Rocco De Vivo, Pablo Gajate, Ashraf Azzabi, Giuseppe Procopio
Journal: Journal of Clinical Oncology (2020)

TPS770 Background: Cabozantinib, an inhibitor of multiple receptor tyrosine kinases including VEGF receptor 2, and MET and AXL receptors, is approved for the treatment of aRCC in the USA and, in Europe, in treatment-naïve patients with intermediate or poor risk, as well as following VEGF-targeted therapy. The METEOR trial investigated cabozantinib as second-line (2L) or later-line therapy and showed improved progression-free survival (PFS), objective response rate and overall survival vs everolimus. Adverse events (AEs) associated with cabozantinib were generally manageable in METEOR; dose interruptions and reductions occurred in 70% and 60% of patients, respectively. Here we present the design of the CASSIOPE study which aims to assess the real-life use of cabozantinib as 2L or third- or later-line (≥ 3L) therapy for aRCC. Methods: CASSIOPE is an ongoing, European, prospective, non-interventional study in adults with aRCC who have received ≥ 1 prior VEGF-targeted therapy and are initiating cabozantinib as 2L or ≥ 3L therapy according to Summary of Product Characteristics. The primary endpoint is the proportion of patients with dose modifications (interruption, reduction or discontinuation) due to AEs. Secondary endpoints include additional drug utilization parameters, effectiveness (overall best response, PFS), and healthcare resource utilization associated with managing treatment-related AEs. Overall, 680 patients (340 on 2L therapy; 340 on ≥ 3L therapy) will be enrolled to assess the 2-sided 95% confidence interval of the primary endpoint with a precision of ± 5%, assuming a 75% dose modification rate and ≤15% of starting doses lower than 60 mg. Visits will be based on the site's clinical practice, with a maximum follow-up of 12 months after treatment initiation, even if treatment is continued. Data collection started in April 2018. As of 9 October 2019, 336 patients have been enrolled. The overall study duration is expected to be 36 months. An interim analysis is planned when ≥ 340 patients have completed ≥ 3 months follow-up from treatment initiation. The study is funded by Ipsen Pharma. Clinical trial information: NCT03419572; EUPAS19464.
Stereotactic body radiotherapy boost toxicity for high and intermediate-risk prostate cancer: Report of a multi-institutional study.
Authors: Irving D. Kaplan, Limor Appelbaum, Nima Aghdam, Jarad Martin, Mark Sidhom, David Pryor, Joseph A. Aronovitz, Anand Mahadevan, Kevin F. Kennedy, Sean P. Collins
Journal: Journal of Clinical Oncology (2020)

365 Background: External beam radiation therapy (EBRT) with androgen suppression (AS) and low dose rate (LDR)brachytherapy boost has been shown to improve biochemical progression free survival in unfavorable intermediate risk and high-risk prostate cancer (PC) compared to EBRT and AS. Excellent rates of local control in locally advanced prostate cancer with EBRT with high dose rate brachytherapy (HDR) boost. Prostate Stereotactic Radiosurgery (SBRT) may be an alternative to brachytherapy in patients with unfavorable intermediate and high-risk PC. Here we report the toxicity of pelvic lymph node/prostate EBRT and SBRT as the radiation boost in a large retrospective cohort. Methods: 473 patients with intermediate or high-risk PC, from the Radiosurgery Society Registry, Beth Israel Deaconess Medical Center, Georgetown University, and 5 Australian centers, were included. Patients received treatment from 3/2004- 9/2018 were the basis of this IRB approved retrospective study. The prostate and pelvis nodes were treated with between 36-50.4 Gy in 1.8/2.0 Gy fractions of radiation therapy EBRT. Patients received a SBRT boost to the prostate. Boost dose was 19-19.5 Gy (range 19-36.25 Gy). 274 and 199 patients presented with unfavorable or high-risk disease. The median follow-up was 33 months (IQR:18-63). Results: 33 deaths of 473 patients occurred in this cohort, 8 of which were caused by PC. There were 13.9% (n=66) acute Grade 1 or 2 GI toxicities (11.8% grade 1, 2.1% grade 2). There were 27.7% (n=131) acute Grade 1 or 2 GU toxicities (19.2% grade 1, 8.5% grade 2). No severe acute GU or GI toxicities were reported. There were 32 (6.8%) Grade 1 and 3 (0.6%) Grade 2 late GI toxicities. There were 9 (1.9%) Grade 3 and 1 (0.2%) Grade 4 late GI toxicities. There were 60 (12.7%) Grade 1 and 23 (4.9%) Grade 2 late GU toxicities. 15 (3.2%) Grade 3, but no Grade 4 late GU toxicity were reported. Conclusions: In this large multi-institutional retrospective cohort SBRT boost to pelvic/prostate EBRT had acceptable acute and late toxicities. The high dose per fraction of SBRT is similar to the dose delivered with HDR. This data raises the hypothesis that SBRT boost should be evaluated in additional clinical trials.
Biomarker analysis of the phase III IPATential150 trial of first-line ipatasertib (Ipat) plus abiraterone (Abi) in metastatic castration-resistant prostate cancer (mCRPC).
Authors: Zhen Shi, Christopher Sweeney, Sergio Bracarda, Cora N. Sternberg, Kim N. Chi, David Olmos, Shahneen Kaur Sandhu, Christophe Massard, Nobuaki Matsubara, Marie-Laurence Harle-Yge, Malgorzata Nowicka, Matthew Wongchenko, Johann S. De Bono
Journal: Journal of Clinical Oncology (2020)

182 Background: IPATential150 is a randomized trial comparing Ipat + Abi vs placebo + Abi in patients (pts) with 1L mCRPC (NCT03072238). We evaluated the potential associations between PTEN loss, genomic alterations, and country of enrollment (East Asian [EAS] vs non-EAS). Methods: Before randomization, tumor samples (archival &gt; 90%) were centrally tested for PTEN loss by VENTANA PTEN (SP218) immunohistochemistry (IHC) assay (N = 1101). Tumor genetic alterations were profiled by Foundation Medicine FoundationOne CDx (F1CDx) NGS assay (n = 735). Results: Of 1101 pts enrolled, 521 (47%) had PTEN loss by IHC. An overall 76% agreement was observed between PTEN IHC and F1CDx. TMPRSS2 fusion, alterations in TP53 and PTEN were most frequent (28%-32%). Alterations in PIK3CA, SPOP, APC, MYC, RAD21, and genes involved in DNA damage repair, including BRCA2, CDK12, ATM, had a 5%-8% prevalence. PTEN loss (IHC) tended to co-occur with genetic alterations in TP53 and TMPRSS2. The prevalence of PTEN loss in EAS vs non-EAS pts was 35% vs 50% by IHC and 15% vs 31% by F1CDx. Alterations in CDK12, BRCA2, SPOP, and MYC were more prevalent in EAS pts, whereas alterations in TMPRSS2, PTEN, and TP53 were more prevalent in non-EAS pts. Conclusions: This analysis reveals molecular heterogeneity in prostate cancer and association between potentially actionable targets. It also suggests that EAS pts with mCRPC have a genetic profile that may be at least quantitatively different from non-EAS pts. Clinical trial information: NCT03072238. [Table: see text]
Organ donation: England will have “opt-out” system from May 2020
Authors: Gareth Iacobucci
Journal: BMJ (2020)

England will move to an “opt-out” system of deemed consent for organ donation from May this year, the government has announced.

The move, which follows a consultation,1 means that all adults in England will be considered to have agreed to donate their organs when they die, unless they have decided that they do not want to be a donor or are in an excluded group.

The new law will bring England into line with Wales, which introduced an opt-out system in December 2015 and now has the highest donation consent rates in the UK.2 Scotland is …
ARN-509 in Men with High Risk Non-Metastatic Castration-Resistant Prostate Cancer
Authors: M.R. Smith, E.S. Antonarakis, C.J. Ryan, W. Berry, N.D. Shore, G. Liu, J. Alumkal, C. Higano, E. Chow-Maneval, D. Rathkopf
Journal: Annals of Oncology (2012)
Challenges in Understanding, Scoring, and Comparing Patients’ Reports
Authors: Mary-Margaret Chren
Journal: JAMA Dermatology (2020)

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
Omalizumab Improves Quality of Life in Patients with Chronic Rhinosinusitis with Nasal Polyps and Comorbid Asthma
Authors: Jonathan Corren, Claus Bachert, Philippe Gevaert, Joaquim Mullol, Joseph Han, Randall Ow, Sanna Toppila-Salmi, Isam Alobid, Derrick Kaufman, Jessica Braid, Monet Howard, Bongin Yoo, Monica Ligueros-Saylan, Lutaf Islam, Theodore Omachi
Journal: Journal of Allergy and Clinical Immunology (2020)
In Aptamers They Trust
Authors: Abhishek Joshi, Manuel Mayr
Journal: Circulation (2018)

Although it has become affordable to sequence the entire human genome, measuring all proteins in a sample as complex as human plasma remains currently out of reach.The plasma proteome has an enormous dynamic range and variability, including splice variants, cleavage products, and posttranslational modifications.Antibody-based techniques have predominated, but other affinity-based techniques such as the SOMAscan aptamer assays from SomaLogic also promise the multiplexed measurement of proteins in a scalable manner.Aptamers are short oligonucleotides that have binding affinity to a single protein.They have been developed by introducing a pool of random sequence oligomers to a target protein, applying affinity selection to separate target-oligomer pairs, and then amplifying the surviving sequences.Iterations of this cycle, called SELEX (Systematic Evolution of Ligands by Exponential Enrichment), increase the specificity and avidity of the surviving oligomers to a target protein, eventually identifying a single oligomer, an aptamer, with high affinity for a protein epitope.Additions of side chains improve the stability of aptamers in biological matrices such as plasma.These modifications also change the binding characteristics of the aptamer, giving the same sequence many different properties.The resulting SOMAmers (Slow Off-Rate Modified Aptamers) can be bound to fluorophores and multiplexed, potentially allowing simultaneous quantification of hundreds to thousands of proteins.The most recent iteration of the platform offers ≈5000 aptamers.The SOMAscan v1.3 platform consists of 1129 aptamers. 1n the current edition of Circulation, Mosley and colleagues 2 use the SOMAscan v1.3 platform in the Framingham Offspring Cohort and report plasma levels of 268 of the measured 1129 proteins to be regulated by single nucleotide polymorphisms (SNPs).Robustness of the findings was demonstrated in the Cooperative Health Research in the Region of Augsburg (KORA) F4 data set, using the same platform.When tested in a third cohort (MDCS [Malmö Diet and Cancer Study]) the strongest gene-protein instruments predicted 60% of a protein's variance, although the median prediction was 8% of the total variance.These gene-protein instruments were used to impute the protein levels of 41 288 previously genotyped individuals in the eMERGE cohort (Electronic Medical Records and Genomics Network), generating the virtual proteome, and their associations with 1128 clinical phecodes derived from electronic health records (EHRs) were assessed.Fifty-five virtual proteins were found to associate with 89 clinical diagnoses in a complex manner; some proteins were associated with more than 1 diagnosis (for example, factor XI was associated with 4 different diagnoses related to venous thrombosis).Some conditions had many associated proteins (for example, thrombosis was predicted by 16 different protein levels).Finally, proteins that were virtually associated
Serial circulating tumor DNA (ctDNA) measurement to predict progression in patients (pts) with advanced urothelial carcinoma (aUC).
Authors: Dario Martin Villamar, Kyrillus Shohdy, Yen Thi Kim Hong Cao, Janson Trieu, Kristin Sedgwick Price, Rebecca Nagy, Ana M. Molina, Scott T. Tagawa, David M. Nanus, Cora N. Sternberg, Guru Sonpavde, Petros Grivas, Nicholas J. Vogelzang, Bishoy Morris Faltas
Journal: Journal of Clinical Oncology (2020)

558 Background: Next-generation sequencing (NGS) of plasma ctDNA is a promising non-invasive method to detect somatic genomic alterations (GAs). We investigated whether serial ctDNA measurements can predict disease progression and map the molecular evolution of advanced UC (aUC) through successive treatments. Methods: We analyzed cohorts from 2 academic centers, WCM and UNLV, with serial (≥2) ctDNA targeted NGS using the Guardant360 panel of 73 genes, ctDNA was collected within four weeks of restaging scans. Non-progressive disease (non-PD) was defined as stable disease or radiological response. Results: Our cohort included 176 individual ctDNA samples (median 3/patient) from 52 patients (38 men), the median age was 69 (range 38-88), 38 pts (73%) had metastatic disease, 20 pts (38.5%) had visceral metastases and 35 pts (67%) received first-line platinum-based combination chemotherapy for aUC. The median number of lines of therapy was 2. 49 pts (94%) had detectable GAs in at least one ctDNA sample. Most commonly identified GAs involved TP53 (67%), PIK3CA, EGFR, and ERBB2 (each in 19%). FGFR3 GAs were identified in 9 pts (17%, 2 FGFR3-TACC3 fusions, and 7 SNVs, including two novel mutations P250R and K650M). The mean variant allele fraction (VAF) significantly decreased in pts with non-PD (80 non-PD events) compared to pts with PD (45 PD events) with a mean VAF decrease of 2.06 % (p&lt; 0.0001). This effect was consistent independent of the number of prior lines of therapy. The mean number of GAs per patient at each time point was significantly decreased in non-PD vs. PD group (2.8 vs. 4.4, p=0.004). Pts with detectable VAF in somatic alterations at any time point during the disease course had shorter overall survival (HR 1.18, 95% CI: 1.08 – 1.28, p&lt;0.0001). Pts with sustained partial or complete responses were more likely to have VAF ≤0.2% suggesting that molecular remission was associated with clinical remission. Conclusions: Serial ctDNA testing is a promising dynamic tool to assess clonal evolution and predict progression in aUC pts.
TAVR at 5 Years — Rematch or Swan Song for Surgery?
Authors: Eric Van Belle
Journal: New England Journal of Medicine (2020)

To become the first-line treatment for patients with aortic stenosis,1 transcatheter aortic-valve replacement (TAVR) must not only mitigate periprocedural events but also be as effective as surgical aortic-valve replacement in the long term. Makkar et al. examined this question and report in this issue of the Journal the 5-year outcomes of the Placement of Aortic Transcatheter Valves (PARTNER) 2 cohort A trial,2 which involved patients at intermediate surgical risk. A total of 2032 patients were stratified according to intended transfemoral or transthoracic access and randomly assigned to undergo TAVR with the second-generation balloon-expandable SAPIEN XT valve or surgical aortic-valve replacement. . . .
Autophagy inhibition changes the disposition of non-viral gene carriers during blood-brain barrier penetration and enhances TRAIL-induced apoptosis in brain metastatic tumor
Authors: Xuhui Wang, Sheng Yin, Man Li, Jingdong Rao, Dandan Wan, Yue Qiu, Qianwen Yu, Xiaoxiao Chen, Zhengze Lu, Yang Long, Zhirong Zhang, Qin He
Journal: Journal of Controlled Release (2020)
The Surgery of the Nose and Accessory Cavities: An Abstract of the Bradshaw Lecture delivered at the Royal College of Surgeons of England on December 1st, 1892
Authors: C. Heath
Journal: BMJ (1892)

THB diseases of the nose have in the last decade obtained an amount of attention on the part of certain members of the profession which their importance seems scarcely to justify.The literature of the subject has grown apace, but 1 say advisedly that the amount of progress bears no proportion to the amount of literary activity displayed since the date of the well-known paper by Dr. Meyer, of Copenhagen, on Adenoid Growths in the Naso-pharyngeal Cavity, communicated in 1869 to the Royal Medical and Chirurgical Society by the late Mr. John Marshall.I do not propose to revive the old contro- versy of " General versus Special," which ran its tedious length some years ago without any particular result; I have, how- ever, to thank the President of the British
Escaping Pandora’s Box — Another Novel Coronavirus
Authors: David M. Morens, Peter Daszak, Jeffery K. Taubenberger
Journal: New England Journal of Medicine (2020)

Escaping Pandora’s Box — Another Novel Coronavirus With luck, public health control measures may be able to put the Covid-19 demons back in the jar. If they do not, we face a daunting challenge equ...