tbuckley/cabot-search huggingface dataset:
A randomized phase III trial of single-agent pemetrexed (P) versus carboplatin and pemetrexed (CP) in patients with advanced non-small cell lung cancer (NSCLC) and performance status (PS) of 2.
Authors: Rogerio Lilenbaum, Mauro Zukin, Jose Rodrigues Pereira, Carlos H. Barrios, Ronaldo De Albuquerque Ribeiro, Carlos Augusto de Mendonça Beato, Yeni Neron do Nascimento, Andre Murad, Fabio A. Franke, Maristela Precivale, Luiz Henrique de Lima Araujo, Clarissa Serodio Da Rocha Baldotto, Fernando Meton Vieira, Isabele Avila Small, Carlos G. M. Ferreira
Journal: Journal of Clinical Oncology (2012)

7506 Background: No standard of care exists for patients with advanced NSCLC and PS 2 and clinical practice ranges from supportive care to combination chemotherapy. Methods: In a Brazilian multicenter phase III randomized trial, advanced NSCLC patients, with any histology at first, amended to non-squamous only, PS 2, no prior chemotherapy, and adequate organ function, were randomized to P alone (500 mg/m2) or CP (AUC 5 + same P) administered every 3 weeks for 4 cycles. Stratification factors included stage (IIIB vs. IV); age (≥70 vs. &lt;70); and weight loss (≥5 kg vs. &lt;5kg). The primary endpoint was overall survival and the study was powered to demonstrate an improvement in median survival from 2.9 to 4.3 months based on a prior CALGB trial. Results: A total of 217 patients were enrolled from 8 centers in Brazil and 1 in the US from April 2008 to July 2011. Twelve patients were ineligible and excluded. The 2 arms (P=102; CP=103) were balanced for patient characteristics. 14 patients had squamous and another 12 had unknown histology. The response rates were P = 10% and CP = 24% (p=0.019). In the ITT population, the median PFS was P = 3.0 mo and CP = 5.9 mo (HR=0.46, 95% CI 0.34; 0.63, p&lt;0.001) and median OS was P = 5.6 mo vs. CP = 9.1 mo (HR=0.57, 95% CI 0.41; 0.79, p=0.001). 1-year survival rates were 22% and 39% respectively. Similar results were seen when squamous patients were excluded from the analysis. Grade ¾ anemia (5.5%; 12%) and neutropenia (2.8%; 5.6%) were more frequent in CP. There were 4 treatment-related deaths in the CP arm. 30% of patients in each arm received 2 nd line therapy Conclusions: Combination chemotherapy with CP significantly improves survival, with acceptable safety, in eligible patients with advanced NSCLC and PS 2, and represents a new standard.
Rap1-GTP Augments TGF-b-Mediated Signaling in T Lymphocytes Via a Mechanism Dependent on the b Chain of LFA-1 Integrin
Authors: Kankana Bardhan, Nikolaos Patsoukis, Alexandra Plessa, Niko Tsopoulidis, Duygu Sari, Lequn Li, Vassiliki A. Boussiotis
Journal: Blood (2015)
Fibroblast Growth Factor 23 Regulation by Systemic and Local Osteoblast-Synthesized 1,25-Dihydroxyvitamin D
Authors: Loan Nguyen-Yamamoto, Andrew C. Karaplis, Rene St–Arnaud, David Goltzman
Journal: Journal of the American Society of Nephrology (2016)

Circulating levels of fibroblast growth factor 23 (FGF23) increase during the early stages of kidney disease, but the underlying mechanism remains incompletely characterized. We investigated the role of vitamin D metabolites in regulating intact FGF23 production in genetically modified mice without and with adenine-induced uremia. Exogenous calcitriol (1,25-dihydroxyvitamin D) and high circulating levels of calcidiol (25-hydroxyvitamin D) each increased serum FGF23 levels in wild-type mice and in mice with global deficiency of the Cyp27b1 gene encoding 25-hydroxyvitamin D 1- α -hydroxylase, which produces 1,25-hydroxyvitamin D. Compared with wild-type mice, normal, or uremic mice lacking Cyp27b1 had lower levels of serum FGF23, despite having high concentrations of parathyroid hormone, but administration of exogenous 1,25-dihydroxyvitamin D increased FGF23 levels. Furthermore, raising serum calcium levels in Cyp27b1-depleted mice directly increased FGF23 levels and indirectly enhanced the action of ambient vitamin D metabolites via the vitamin D receptor. In chromatin immunoprecipitation assays, 25-hydroxyvitamin D promoted binding of the vitamin D receptor and retinoid X receptor to the promoters of osteoblastic target genes. Conditional osteoblastic deletion of Cyp27b1 caused lower serum FGF23 levels, despite normal circulating levels of vitamin D metabolites. In adenine-induced uremia, only a modest increase in serum FGF23 levels occurred in mice with osteoblastic deletion of Cyp27b1 (12-fold) compared with a large increase (58-fold) in wild-type mice. Therefore, in addition to the direct effect of high circulating concentrations of 25-hydroxyvitamin D, local osteoblastic conversion of 25-hydroxyvitamin D to 1,25-dihydroxyvitamin D appears to be an important positive regulator of FGF23 production, particularly in uremia.
A Closer Inspection of the Number Needed to Biopsy
Authors: Michael A. Marchetti, Stephen W. Dusza, Allan C. Halpern
Journal: JAMA Dermatology (2016)

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
Long-term treatment of giant cell tumors of bone (GCTB) with denosumab: a two institutions 8-year experience.
Authors: Neal Shiv Chawla, Madhuri Sudan, Imran Syed, Sant P. Chawla, Stefano Ferrari, Piero Picci, Emanuela Marchesi, Martina Piccinni Leopardi, Kamalesh Kumar Sankhala, Prarthana Parthasarathy, William Esteves Mendanha, Anna Paioli, Justin Daneshrad, Emanuela Palmerini
Journal: Journal of Clinical Oncology (2016)

11021 Background: Giant cell tumours of bone (GCTB’s) are RANK-ligand (RANK-L) positive, aggressive and progressive osteolytic tumors. Denosumab, a RANK-L inhibitor, was FDA-approved for adults and skeletally mature adolescents with GCTBs that is unresectable or where surgical resection is likely to result in severe morbidity. GCTB’s. Data on long-term “Denosumab,120 mg-monthly-schedule” are lacking. We present an 8-year study, conducted in 2 referral centers. Methods: All GCTB’s receiving Denosumab, 120 mg on days 1, 8, 15, 29, and every 4-weeks thereafter, from 2006 to 2014, were included. Clinical responses and long-term side effects were assessed. Results: 97 cases identified, male/female 40/57, median age 35 years (range: 13-76 years), 15% presented lung metastases, 43% were relapsed after previous surgery. Median time on treatment was 23 months (4 - 94 months). Median highest pain (VAS scale) was 4 (0-10), and decreased to 2 (0-10), with 67% with complete pain resolution after 3 months in 67% of the cases. One of the patients experienced increased tumor growth, with sustained tumor control for all others (RECIST criteria do not apply due to intra-osseous only disease and massive denosumab-induced calcification). Tumor control was also demonstrated in 6/6 localised cases undergoing denosumab re-challenge for relapse. Adverse events: 6% of patients developed osteonecrosis of jaw (ONJ), 6% mild peripheral neuropathy, 4 skin rash, and 1 an atypical fracture. For the 6 patients with ONJ the median time on treatment was 37 months (6-76), the median age was 50 years (22-76); 5/6 ONJs occurred after 2 years of Densoumab, while in 1 patient, with dental comorbidities, ONJ was documented after 6 months. Outcome: 41% are still on treatment, 35% completed therapy, 9% were lost to follow-up, 6% withdrew consent, 5% stopped denosumab for ONJ, 2% went
Fibrosis and Mortality in Patients With Dilated Cardiomyopathy
Authors: Andrea Barison, Pier Giorgio Masci, Michele Emdin
Journal: JAMA (2013)

Our website uses cookies to enhance your experience. By continuing to use our site, or clicking "Continue," you are agreeing to our Cookie Policy | Continue JAMA HomeNew OnlineCurrent IssueFor Authors Publications JAMA JAMA Network Open JAMA Cardiology JAMA Dermatology JAMA Health Forum JAMA Internal Medicine JAMA Neurology JAMA Oncology JAMA Ophthalmology JAMA Otolaryngology–Head & Neck Surgery JAMA Pediatrics JAMA Psychiatry JAMA Surgery Archives of Neurology & Psychiatry (1919-1959) Podcasts Clinical Reviews Editors' Summary Medical News Author Interviews More JN Learning / CMESubscribeJobsInstitutions / LibrariansReprints & Permissions Terms of Use | Privacy Policy | Accessibility Statement 2023 American Medical Association. All Rights Reserved Search All JAMA JAMA Network Open JAMA Cardiology JAMA Dermatology JAMA Forum Archive JAMA Health Forum JAMA Internal Medicine JAMA Neurology JAMA Oncology JAMA Ophthalmology JAMA Otolaryngology–Head & Neck Surgery JAMA Pediatrics JAMA Psychiatry JAMA Surgery Archives of Neurology & Psychiatry Input Search Term Sign In Individual Sign In Sign inCreate an Account Access through your institution Sign In Purchase Options: Buy this article Rent this article Subscribe to the JAMA journal
Heightened Proteolysis of Plasma ADAMTS13 Antigen in Patients with Thrombotic Thrombocytopenic Purpura.
Authors: Hideo Yagi, Masanori Matsumoto, Taka-aki Iwamoto, Hiromichi Ishizachi, Hitomi Nishimura, Ayami Isonishi, Kenji Soejima, Tomohiro Nakagaki, Toshio Mori, Yoshihiro Fujimura
Journal: Blood (2004)
Long-term survival of patients with metastatic renal cell carcinoma (mRCC) treated with targeted therapy (TT) without cytoreductive nephrectomy (CN).
Authors: S. L. Richey, S. H. Culp, E. Jonasch, P. G. Corn, L. C. Pagliaro, P. Tamboli, K. Patel, S. F. Matin, N. M. Tannir
Journal: Journal of Clinical Oncology (2011)

346 Background: We recently reported on 188 patients (pts) with mRCC treated with TT without CN [Richey et al, J Clin Oncol 28:15s, 2010 (suppl; abstr 4613); Annals of Oncology- in press]. We report here outcome data on pts who survived &gt; 24 months (mos). Methods: We retrospectively reviewed records of patients with mRCC who received TT without CN and survived longer than 24 mos from treatment initiation. Pts did not undergo CN due to medical comorbidity, unresectable primary tumor, heavy disease burden, or patient preference. Kaplan-Meier methods were used to estimate median overall survival (OS). Long-term complications related to therapy were evaluated. Results: 22 pts were identified meeting the inclusion criteria. Median follow-up was 30.4 mos (range, 24.1- 68.7), with median OS time of 34.1 mos (95% CI: 30.2, 37.2). Median time on therapy (TOT) was 25.3 mos (IQR: 13.7, 28.5). Six pts (27.3%) were alive at the time of analysis, with median TOT of 26.9 mos (range: 13.7, 62.5) (IQR: 24.6, 33.4). Eastern Cooperative Oncology Group performance status was 0 or 1 in 86% of pts. Ten (45%) and 12 (55%) pts had intermediate- and poor-risk disease by Heng et al criteria (JCO 2009), respectively. Patients received the following types of TT: sunitinib 14 (63.6%), sorafenib 13 (59.1%), temsirolimus 5 (22.7%), bevacizumab 5 (22.7%), pazopanib 3 (13.6%), everolimus 4 (18.2%), erlotinib 3 (13.6%), investigational targeted agent 1 (4.6%). Four (18.2%), 5 (22.7%), and 13 (59.1%) pts received 1, 2, or ≥ 3 different therapies, respectively. During treatment with TT, 6 pts (27.3%) developed hypertension, 6 pts (27.3%) developed hypothyroidism, 2 pts (9.1%) developed congestive heart failure, 1 pt (4.6%) developed stroke. No pts developed bleeding or myocardial infarction. By radiographic assessment of best primary tumor response, 4 (18.2%) pts had a partial response (≥30% decrease), 10 (45.5%) exhibited a decrease &lt;30%, and 6 (27.3%) had stable or increased size of the primary tumor. Conclusions: These data highlight the potential for long-term survival of patients with mRCC treated with TT without CN, and underscore the challenges in managing therapy-related long-term adverse events. No significant financial relationships to disclose.
Retrospective Study of the Incidence and Risk Factors for Hematological Malignancies in Patients with Hepatitis B Virus Infection
Authors: Erin Jou, Carmen KM Cheung, Ryan CY Ho, Diwakar Mohan, Uriel Felsen, Henny H Billett, Anthony T.C. Chan, Edwin P Hui, Radha Raghupathy
Journal: Blood (2014)
Management of patients with heart failure using education or education & yelephone or telephone in Cyprus (MEETTinCy) trial. Preliminary results
Authors: Ekaterini Lambrinou, Fotini Kalogirou, A Protopapas, Elizabeth Papathanassoglou, V. Barberis, Panayota A. Sourtzi, Chryssoula Lemonidou, Nicos Middleton
Journal: European Journal of Heart Failure (2013)
The Transcription Factor IRF8 is a Key Transcription Factor for Basophil Development
Authors: Daisuke Kurotaki, Haruka Sasaki, Naoki Osato, Izumi Sasaki, Chika Kaneda, Hideaki Sato, Akira Nishiyama, Tsuneyasu Kaisho, Hiroyuki Aburatani, Herbert C. Morse, Keiko Ozato, Tomohiko Tamura
Journal: Blood (2013)
Selenium Supplementation and Cancer Rates
Authors: Jay S. Parker
Journal: JAMA (1997)

<h3>To the Editor.</h3> —I have questions regarding the article by Clark et al.<sup>1</sup>Other selenium studies I have read generally use generic forms of selenium: selenomethionine or sodium selenite. The study by Clark et al<sup>1</sup>uses a commercial product: high-selenium yeast tablets from Nutrition 21. Nutrition 21 manufactures selenium supplements for distribution to health food stores. The use by Clark et al of Nutrition 21 selenium tablets could be interpreted as an endorsement. Already Nutrition 21 distributors are citing the study by Clark et al in sales promotions for Nutrition 21 selenium tablets. An independent chemical supplier could have made up selenomethionine tablets for this study, thereby avoiding commercial involvement. Many people cannot tolerate even small amounts of yeast. This fact may have caused the gastrointestinal upset that led some of the research subjects to withdraw from the study. The study by Clark et al states that 200 μg of selenium
Abstract 18430: Human Molecular Genetic and Functional Studies Identify TRIM63, Encoding Muscle RING Finger Protein 1, as a Novel Gene for Human Hypertrophic Cardiomyopathy
Authors: Suet Nee Chen, Grazyna Czernuszewicz, Raffaella Lombardi, Jianping Jin, James Willerson, Ali J Marian
Journal: Circulation (2012)

Rationale: A delicate balance between protein synthesis and degradation maintains cardiac size and function. TRIM63 encoding Muscle RING Finger 1 (MuRF1) maintains muscle protein homeostasis by tagging the sarcomere proteins with ubiquitin for subsequent degradation by the Ubiquitin-Proteasome System (UPS). Objectives: To determine the pathogenic role of TRIM63 in human hypertrophic cardiomyopathy (HCM). Methods and Results: Sequencing of TRIM63 gene in 302 HCM probands (250 Caucasians) and 339 controls (262 Caucasians) led to identification of two missense (p.A48V and p.I130M) and a deletion (p.Q247X) variants exclusively in the HCM probands. These three variants were absent in 751 additional controls screened by TaqMan assays. Likewise, rare variants were enriched in the Caucasian HCM population (11/250, 4.4% vs. 3/262, 1.1%, respectively, p=0.024). Expression of the mutant TRIM63 was associated with mislocalization of TRIM63 to sarcomere Z disks, impaired auto-ubiquitination, reduced ubiquitinylation and UPS-mediated degradation of myosin heavy chain 6, cardiac myosin binding protein C, calcineurin (PPP3CB), and p-mTOR in adult cardiac myocytes. Induced expression of the mutant TRIM63 in the mouse heart was associated with cardiac hypertrophy, activation of the mTOR-S6K and calcineurin pathways and expression of the hypertrophic markers, which were normalized upon turning off expression of the mutant protein. Conclusions: TRIM63 mutations, identified in patients with HCM, impart loss-of-function effects on E3 ligase activity and are likely causal mutations in HCM. The findings implicate impaired protein degradation in the pathogenesis of HCM.
Treatment of periodontal disease in older adults
Authors: Stefan Renvert, G. Rutger Persson
Journal: Periodontology 2000 (2016)

Within the next 40 years the number of older adults worldwide will more than double. This will impact periodontal treatment needs and presents a challenge to health-care providers and governments worldwide, as severe periodontitis has been reported to be the sixth most prevalent medical condition in the world. Older adults (≥ 80 years of age) who receive regular dental care retain more teeth than those who do not receive such care, but routine general dental care for these individuals is not sufficient to prevent the progression of periodontitis with the same degree of success as in younger individuals. There is a paucity of data on the efficacy of different periodontal therapies for older individuals. However, considering the higher prevalence of chronic medical conditions seen in older adults, it cannot be assumed that periodontal therapy will yield the same degree of success seen in younger individuals. Furthermore, medications can influence the status of the periodontium and the delivery of periodontal care. As an example, anticoagulant drugs are common among older patients and may be a contraindication to certain treatments. Newer anticoagulants will, however, facilitate surgical intervention in older patients. Furthermore, prescription medications taken for chronic conditions, such as osteoporosis and cardiovascular diseases, can affect the periodontium in a variety of ways. In summary, consideration of socio-economic factors, general health status and multiple-drug therapies will, in the future, be an important part of the management of periodontitis in older adults.
Head of radiology school to be re-appointed after complaints from royal college
Authors: Gareth Iacobucci
Journal: BMJ (2016)

Health Education England (HEE) has agreed to rerun the process of appointing a head to a regional training school for radiologists, after the Royal College of Radiologists (RCR) criticised the decision to appoint a non medic to the role.

The college was unhappy that it was not consulted about the “ill informed and ill conceived” decision to appoint a radiographer to the post of head of the Yorkshire and the Humber School of Radiology.1 …
Poster Session 1: Practice Issues; Signal Transduction and Nuclear Receptors
Authors: Aisling Considine, Suman Verma, Kath Oakes, Kate Childs, Sarah Knighton, Andrew Ayers, Abid Suddle, Kosh Agarwal, Colina Yim, Cheryl Dale, Geri Hirsch, Jo-Ann Ford, Caro- Lyn Klassen, Carolyn Klassen, Heather Johnson, Emily Graham, Michael Dunn, Kapil Chopra, Anna Moles, Jacqueline Butterworth, Jill Hunter, Ana Sanchez, Dina Tiniakos, Derek Mann, Fiona Oakley, Neil Perkins
Journal: Hepatology (2015)

Background: The advent of directly acting anti-virals (DAA) has led to simplified HCV regimens with increased efficacy rates and better tolerability.The high adherence seen in clinical trials may not translate to real life populations.Optimal adherence is critical to protect patients from treatment failure and resistance.Aim: To identify potential factors which may contribute to sub-optimal adherence in a population with decompensated cirrhosis.Methods: HCV patients eligible for access to a 12 week treatment regimen under a UK NHSE mandated access scheme were consented to complete a baseline questionnaire capturing data on sociodemographics, clinical status and perceptions of illness.Adherence assessments at treatment weeks 4, 8 and 12 with pill counts and a Morisky Medication Adherence Scale were undertaken.Suboptimal adherence (SA) was defined as any report or pill count which indicated a delayed (>2hrs) or missed dose of anti-viral.Descriptive statistic and multivariate regression methods were utilised for analysis.Results: 80% (n=47) of the cohort had reached SVR 12 and are included in the adherence analysis.85%received sofosbuvir/ledipasvir and 15% sofosbuvir with daclatasvir.All patients received ribavirin and had been attending specialist hepatology services for >12 months.43%(n=20) of patients demonstrated SA during their treatment.Multivariate analysis demonstrated that any non-attendance during treatment and a 'limited support network' predicted higher rates of SA (p<0.05).In the SA group, 80% were taking >3 medications (vs 74% in adherent group).The average MELD score was 15 in the SA group (vs 13 in adherent group).80% of SA was associated with symptoms secondary to disease stage not reflected by the MELD.SA secondary to side effects of therapy was not identified.85% of the SA group achieved SVR12.Failure to achieve SVR was seen in those with SA adherence at all assessment points (weeks 4, 8 and 12).Conclusions: Our initial results demonstrate that despite an intensive adherence focused multi-disciplinary approach, SA occurs in decompensated HCV cirrhotic patients.Acceptable SVR rates were achieved in this population.Further research is warranted to develop strategies which maximise adherence in all HCV populations.
Optimal Time Points for Scintigraphic Imaging of Pleuroperitoneal Shunts
Authors: Matthew F. Covington, Gagandeep Choudhary, Ryan J. Avery, Elizabeth A. Krupinski, Phillip H. Kuo
Journal: Clinical Nuclear Medicine (2016)

Nuclear imaging can confirm pleuroperitoneal shunt as the cause of pleural effusion. No society guidelines exist for scintigraphic pleuroperitoneal shunt detection. Our institutional protocol was evaluated to determine optimal imaging time points for shunt detection.Pleuroperitoneal shunt studies over 4 years were blindly reviewed by 2 nuclear radiologists. Data from blinded review included presence or absence of pleuroperitoneal shunt, laterality of shunt and time points for shunt detection.Chart review yielded 30 studies. Three cases were excluded because of improper injection. Imaging was positive for pleuroperitoneal shunt in 81% (22/27) of cases. In positive cases, activity was identified in the right hemithorax in 82% (18/22), left hemithorax in 9% (2/22), and bilaterally in 9% (2/22). One-hour imaging demonstrated 91% (20/22) of positive cases. The remaining 2 positive cases were negative at 1 hour but positive after 4 hours. No study was negative at 1 and 4 hours and positive at 24 hours. All negative cases (5/27) were confirmed on 24-hour imaging.The majority of positive pleuroperitoneal shunt examinations will demonstrate activity in the right hemithorax on 1-hour imaging. Although no case was negative at 1 and 4 hours and positive at 24 hours, imaging at 24 hours may still be necessary to confirm absence of shunt. Therefore, optimal imaging time points consist of early 1-hour and delayed 24-hour images if the 1-hour time point was negative. The 4-hour time point may be considered optional, thereby potentially optimizing patient safety and resource utilization.