tbuckley/cabot-search huggingface dataset:
Temporal trends among survivors of rhabdomyosarcoma: A report from the Childhood Cancer Survivor Study (CCSS).
Authors: Pooja Hingorani, Mingjuan Wang, Deokumar Srivastava, Paul C. Nathan, Kevin C. Oeffinger, Yutaka Yasui, Wendy M. Leisenring, Rebecca M. Howell, Emily L. Mueller, Todd M. Gibson, Suzanne L. Wolden, Kari L. Bjornard, William H. Meyer, Carola A. S. Arndt, Leslie L. Robison, Daniel M. Green, Gregory T. Armstrong, Kirsten K. Ness
Journal: Journal of Clinical Oncology (2019)

11570 Background: Intergroup Rhabdomyosarcoma Study Group (IRSG) protocols included treatment modifications, which may have ameliorated late health outcomes for rhabdomyosarcoma (RMS) survivors treated in more recent era. Methods: We evaluated chronic health conditions (CHCs) and late mortality ( &gt; 5 years from diagnosis) among survivors treated 1970-1990 (IRSG I-III) and 1991-1999 (IRSG IV), and associations with specific treatments to identify treatment-related factors for adverse outcomes. Associations between treatments and CHCs and mortality were evaluated using Fine and Gray’s proportional hazards method accounting for competing risks. Results: 856 survivors treated 1970-90 (median diagnosis age 5.4 years [0- 20]) and 306 treated 1991-99 (median diagnosis age 5.5 years [0-20]) were included. Significant exposure differences between eras included higher percentage (53% vs. 17%, p &lt; 0.01) receiving ≥ 20gm/m 2 cumulative alkylators in 1991-99, but more receiving platinums (13% vs 5%, p &lt; 0.01) and abdomen/ pelvis radiation (29% vs. 23%, p = 0.04) in 1970-90. 20-year cumulative incidence for any (40% vs. 28%, p &lt; 0.01), ≥2 (16% vs. 7%, p &lt; 0.01), and endocrine (8% vs. 2.5%, p &lt; 0.01) grade 3-5 CHCs was higher in 1970-90 compared to 1991-99. The hazard ratio (HR) for any (HR 0.7, 95% Confidence Interval [CI] 0.55-0.9), ≥2 (HR 0.38, 95% CI 0.22-0.66) and endocrine (HR 0.25, 95% CI 0.09-0.67) grade 3-5 CHC was lower for 1991-99 survivors than 1970-90. The effect of era (1991-99 vs 1970-90, HR 0.73; 95% CI 0.59-0.91) on CHC was not attenuated when treatment variables were added to multivariable model. Exposures with increased risk of grade 3-5 CHC included platinums (hearing, HR 2, 95% CI 1.07-3.8), anthracycline ≥250mg/m 2 (cardiovascular, HR 2.7, 95% CI 1.2-6) and abdomen/ pelvis radiation (second malignant neoplasms, HR 2.1, 95% CI 1.1-4, gastrointestinal, HR 7.4, 95% CI 3.5-16 and endocrine, HR 2.5, 95% CI 1.4-4.4). Gonadal dysfunction was the most common endocrine CHC. There was no difference in all cause or cause-specific mortality between the two cohorts. Conclusions: RMS survivors from the IRSG IV era are at reduced risk for late onset chronic health conditions compared to previous era.
Abstract 10911: Collagen Biomarkers Are Associated With Decline in Renal Function Independently of Blood Pressure and Other Cardiovascular Risk Factors: The MESA Study
Authors: Daniel A Duprez, Myron D Gross, Joachim H Ix, Carmen Peralta, Jorge R Kizer, Steven Shea, David R Jacobs
Journal: Circulation (2018)

Background: Kidney function decline is associated with underlying renal fibrosis. We studied the association of two major circulating collagen biomarkers, Collagen Type I Carboxy Terminal Telopepti...
Debate Sparks Over LATE, a Recently Recognized Dementia
Authors: Jennifer Abbasi
Journal: JAMA (2019)

Our website uses cookies to enhance your experience. By continuing to use our site, or clicking "Continue," you are agreeing to our Cookie Policy | Continue JAMA HomeNew OnlineCurrent IssueFor Authors 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
AB0061 INVESTIGATING THE ROLE OF TGF-B AND FATIGUE IN CHRONIC FATIGUE SYNDROME
Authors: Beth Dibnah, Emmanuella Traianos, Jessica Tarn, Dennis Lendrem, Wan Fai Ng
Journal: Annals of the Rheumatic Diseases (2019)

<h3>Background:</h3> Chronic fatigue syndrome (CFS) is estimated to affect up to 5% of people in Europe and is more common in women than men. It is characterised by unexplained fatigue, post-exertional malaise and a range of other symptoms. Recent studies indicate potential immune dysfunction in CFS, specifically regarding cytokines and the adaptive behavioural response. <h3>Objectives:</h3> This study aims to investigate serum transforming growth factor-beta (TGF-β) and the expression of the TGF-β Receptor 1 (TGFBR1) and TGF-β Receptor 2 (TGFBR2) genes, in relation to the fatigue associated with CFS. <h3>Methods:</h3> Serum active and total TGF-β concentrations were measured in 117 CFS patients and 40 HCs using a TGF-β responsive luciferase bioassay. Expression levels of TGFBR1 and TGFBR2 were analysed using quantitative PCR. Fatigue was measured using the fatigue impact scale (FIS)<sup>1</sup>. FIS was categorised into three groups; ‘mild’ (0-80), ‘moderate’ (81-120) and ‘severe’ (121-160). Linear and ordinal regressions were performed on the continuous FIS and FIS categories respectively. <h3>Results:</h3> Serum TGF-β concentrations in the CFS group did not differ significantly compared with the HC group (p=0.58). TGF-β concentrations showed no correlation with disease duration but there was a trend towards decreased TGF-β with increasing symptom duration. There were no significant differences between the levels of TGFBR1 and TGFBR2 in any of the fatigue groups, or between HCs. Active TGF-β concentrations were significantly elevated in the ‘severe’ FIS group compared to the ‘mild’ FIS group (p=0.04). Active/total TGF-β levels were significantly higher in the ‘severe’ FIS group than the ‘mild’ and ‘moderate’ FIS groups (p=0.02, p=0.03 respectively). <h3>Conclusion:</h3> These data suggest no differences in serum concentrations of TGF-β or expression of TGFBR1 and TGFBR2, between the HC and CFS groups. It also suggests no differences in expression levels of TGFBR1/2 between any of the CFS fatigue groups. However, active/total TGF-β levels were increased in more severely fatigued patients based on FIS. This finding could be due to higher levels of circulating TGF-β, or increased amounts of TGF-β activation. Further work is necessary to confirm this finding in a larger cohort of CFS patients, and to explore how this increase in TGF-β relates to fatigue. <h3>References</h3> [1] Fisk JD, Ritvo PG, Ross L, Haase DA, Marrie TJ, Schlech WF. Measuring the functional impact of fatigue: initial validation of the fatigue impact scale. Clinical infectious diseases : an official publication of the Infectious Diseases Society of America. 1994;18Suppl 1:S79-83. <h3>Disclosure of Interests:</h3> None declared
Low-Level Inhibition of Hsp90 Forces Cells to Tip Their (Antigenic) Hand
Authors: Pramod K. Srivastava, Margaret K. Callahan
Journal: Clinical Cancer Research (2019)

Low-level inhibition of hsp90 enhances the antigenicity of cells whereas high-level inhibition diminishes antigenicity. The mechanism(s) by which hsp90 determines antigenicity are only partially clear. Regardless, these observations have profound implications in protein trafficking and antigen presentation and suggest a novel way to enhance the potency of existing anticancer agents.See related article by Jaeger et al., p. 6392.
Pathogenesis and management of fracture-related infection
Authors: M. Depypere, M. Morgenstern, R. Kuehl, E. Senneville, T.F. Moriarty, W.T. Obremskey, W. Zimmerli, A. Trampuz, K. Lagrou, W-J. Metsemakers
Journal: Clinical Microbiology and Infection (2019)
Recent progress in drug delivery
Authors: Chong Li, Jiancheng Wang, Yiguang Wang, Huile Gao, Gang Wei, Yongzhuo Huang, Haijun Yu, Yong Gan, Yongjun Wang, Lin Mei, Huabing Chen, Haiyan Hu, Zhiping Zhang, Yiguang Jin
Journal: Acta Pharmaceutica Sinica B (2019)

Drug delivery systems (DDS) are defined as methods by which drugs are delivered to desired tissues, organs, cells and subcellular organs for drug release and absorption through a variety of drug carriers. Its usual purpose to improve the pharmacological activities of therapeutic drugs and to overcome problems such as limited solubility, drug aggregation, low bioavailability, poor biodistribution, lack of selectivity, or to reduce the side effects of therapeutic drugs. During 2015–2018, significant progress in the research on drug delivery systems has been achieved along with advances in related fields, such as pharmaceutical sciences, material sciences and biomedical sciences. This review provides a concise overview of current progress in this research area through its focus on the delivery strategies, construction techniques and specific examples. It is a valuable reference for pharmaceutical scientists who want to learn more about the design of drug delivery systems.
Budesonide-formoterol reliever therapy versus maintenance budesonide plus terbutaline reliever therapy in adults with mild to moderate asthma (PRACTICAL): a 52-week, open-label, multicentre, superiority, randomised controlled trial
Authors: Jo Hardy, Christina Baggott, James Fingleton, Helen K Reddel, Robert J Hancox, Matire Harwood, Andrew Corin, Jenny Sparks, Daniela Hall, Doñah Sabbagh, Saras Mane, Alexandra Vohlidkova, John Martindale, Mathew Williams, Philippa Shirtcliffe, Mark Holliday, Mark Weatherall, Richard Beasley, Andrew Corin, Liz Dronfield, Colin Helm, Tracy Paterson, Bhuwan Poudel, Malcolm Dyer, Christine Jasinski, Davitt Sheahan, Pamela Sheahan, Nick Gailer, Jan Van Zuilen, Andy Basa, Christine Devereaux, Karin Egan, Sneha Haughey, Rodney Marks, Dirk Venter, Hank Zhang, Karen Trevithick, Mike Williams, Philippa Williams, Christina Baggott, Richard Beasley, Irene Braithwaite, Alexandra Eathorne, Stefan Ebmeier, James Fingleton, Daniela Hall, Jo Hardy, Matire Harwood, Mark Holliday, Claire Houghton, Saras Mane, John Martindale, Karen Oldfield, Janine Pilcher, Doñah Sabbagh, Philippa Shirtcliffe, Suzanne Snively, Jenny Sparks, Alexandra Vohlidkova, Mathew Williams, Patrick Collins, Summer Hassan, Annika Lam, Claudette Lionnet, Barney Montgomery, Liz Smaill, Stella Moon, Dean Quinn, Elena Bayly-McCredie, Chris Millar-Coote, Dean Millar-Coote, Jim Reid, Anna Samuel, Nicola Burton, Tina Mullard, Tyronne Tranquilino, Edward Watson, Jill Bell, Rachel Harris, John Richmond, Sue Smith, Brent Krivan, Cheryl Robertson, Robert J Hancox, Mark Weatherall, Sue Glensor, Dermot O'Connor, Anne-Christine Porrachia, Helen K Reddel
Journal: The Lancet (2019)
Response to Comment on Elliott et al. Prevalence and Prognosis of Unrecognized Myocardial Infarction in Asymptomatic Patients With Diabetes: A Two-Center Study With Up to 5 Years of Follow-up. Diabetes Care 2019;42:1290–1296
Authors: Michael D. Elliott, John F. Heitner, Han Kim, Edwin Wu, Michelle A. Parker, Daniel C. Lee, Dixon B. Kaufman, Robert O. Bonow, Robert Judd, Raymond J. Kim
Journal: Diabetes Care (2019)

We greatly appreciate the comments by Milei et al. (1) about our investigation of the prevalence and prognostic significance of unrecognized myocardial infarction (MI) on delayed-enhancement MRI imaging (2). The combination of silent presentation and adverse prognosis associated with unrecognized MI in patients with diabetes presents both a diagnostic and therapeutic challenge. It has been suggested that the high cardiac risk associated with diabetes may, in part, be attributed to the fact that coronary artery disease in this patient population is notoriously …
Safety and Preliminary Antitumor Activity of the Anti-PD-1 Monoclonal Antibody REGN2810 Alone or in Combination with REGN1979, an Anti-CD20 x Anti-CD3 Bispecific Antibody, in Patients with B-Lymphoid Malignancies
Authors: Max S. Topp, Peter Borchmann, Nina D. Wagner-Johnston, Mariano Provencio, Raul Cordoba, Kyriakos Papadopoulos, Alejandro Martín, Carlos Grande, Deepa Jagadeesh, Nehal Lakhani, Sven de Vos, Anthony R. Mato, Uta Brunnberg, Sebastian Scholl, Christiane Pott, Sarah C Rutherford, Johannes Duell, Lieve Adriaens, Melanie Ufkin, Ana Kostic, Anne Josee Paccaly, Bo Gao, Israel Lowy, David Sternberg, Cecilia Carpio
Journal: Blood (2017)
Circulating Tumor DNA Sequencing Analysis of Gastroesophageal Adenocarcinoma
Authors: Steven B. Maron, Leah M. Chase, Samantha Lomnicki, Sara Kochanny, Kelly L. Moore, Smita S. Joshi, Stacie Landron, Julie Johnson, Lesli A. Kiedrowski, Rebecca J. Nagy, Richard B. Lanman, Seung Tae Kim, Jeeyun Lee, Daniel V.T. Catenacci
Journal: Clinical Cancer Research (2019)

Abstract Purpose: Gastroesophageal adenocarcinoma (GEA) has a poor prognosis and few therapeutic options. Utilizing a 73-gene plasma-based next-generation sequencing (NGS) cell-free circulating tumor DNA (ctDNA-NGS) test, we sought to evaluate the role of ctDNA-NGS in guiding clinical decision-making in GEA. Experimental Design: We evaluated a large cohort (n = 2,140 tests; 1,630 patients) of ctDNA-NGS results (including 369 clinically annotated patients). Patients were assessed for genomic alteration (GA) distribution and correlation with clinicopathologic characteristics and outcomes. Results: Treatment history, tumor site, and disease burden dictated tumor-DNA shedding and consequent ctDNA-NGS maximum somatic variant allele frequency. Patients with locally advanced disease having detectable ctDNA postoperatively experienced inferior median disease-free survival (P = 0.03). The genomic landscape was similar but not identical to tissue-NGS, reflecting temporospatial molecular heterogeneity, with some targetable GAs identified at higher frequency via ctDNA-NGS compared with previous primary tumor-NGS cohorts. Patients with known microsatellite instability-high (MSI-High) tumors were robustly detected with ctDNA-NGS. Predictive biomarker assessment was optimized by incorporating tissue-NGS and ctDNA-NGS assessment in a complementary manner. HER2 inhibition demonstrated a profound survival benefit in HER2-amplified patients by ctDNA-NGS and/or tissue-NGS (median overall survival, 26.3 vs. 7.4 months; P = 0.002), as did EGFR inhibition in EGFR-amplified patients (median overall survival, 21.1 vs. 14.4 months; P = 0.01). Conclusions: ctDNA-NGS characterized GEA molecular heterogeneity and rendered important prognostic and predictive information, complementary to tissue-NGS. See related commentary by Frankell and Smyth, p. 6893
Percutaneous radiofrequency ablation of lung tumours: Results in first 100 consecutive patients
Authors: J. C. Zhu, T. D. Yan, K. Ng, D. Glenn, D. L. Morris
Journal: Journal of Clinical Oncology (2007)

7714 Background: Treatment modalities for patients with primary and secondary lung malignancies who are not surgical candidates are limited. Radiofrequency ablation is a minimally invasive, lung sparing therapeutic alternative that may provide local disease control for these patients. The study reported our experience with first 100 consecutive patients who underwent radiofrequency ablation of their lung tumours. Methods: From November 2000 to December 2006, the clinical and treatment-related information regarding the 100 consecutive patients (58 males, mean age of 65 years) with 240 lung tumours treated by radiofrequency ablation were collected prospectively. Radiofrequency ablation was performed percutaneously under CT guidance with local anaethesiologic assistance and conscious sedation using a RITA Starbust XL electrode. The patients were hospitalized overnight and followed at one week, one month and then every three months with CT to evaluate treatment outcome and complications. Results: Five patients had primary lung carcinoma while the remaining patients had pulmonary metastases from extra-thoracic malignancies, with colorectal cancer being the most common primary site (68%), followed by renal cell carcinoma (8%) and uterine leiomyosarcoma (5%). The mean number of pulmonary lesions ablated was 2.4 per patient; the mean size of lesion ablated was 2.2 cm in diameter. Fifteen patients had second-time RFA; 4 patients underwent third- or fourth-time RFA for pulmonary recurrence. There was no post-procedural mortality and the overall morbidity rate was 42%. The most common complication was pneumothorax, which occurred in of 31% of procedures (n=39/127) with 20 (16%) requiring chest tube placement. After a median follow-up of 24 months (range 1 to 70 months), 72% of RFA treated lesions did not progress. The overall median disease-free interval was 13 months, with 1-, 3- and 5- year disease-free survival of 55%, 22% and 7% respectively. The overall median survival was 34 months with 1-, 3- and 5-year- survival of 85%, 49% and 33% respectively. Conclusions: Percutaneous radiofrequency ablation is an emerging therapy with promising results when surgical resection of pulmonary malignancy cannot be performed. No significant financial relationships to disclose.
Association of Restless Legs Syndrome With Risk of Suicide and Self-harm
Authors: Sheng Zhuang, Muzi Na, John W. Winkelman, Djibril Ba, Chun-Feng Liu, Guodong Liu, Xiang Gao
Journal: JAMA Network Open (2019)

<h3>Importance</h3> Restless legs syndrome (RLS) is a common neurologic disorder that has been previously found to be associated with higher odds of suicidal ideation. In the context of the increasing suicide rate in the United States, the evidence regarding the association between RLS and the risk of suicide and self-harm is limited. <h3>Objective</h3> To investigate the association between RLS and risk of suicide and self-harm. <h3>Design, Setting, and Participants</h3> This cohort study was performed using Truven Health MarketScan national claims data from 2006 to 2014; the baseline data were from 2006 to 2008, and the follow-up data covered 6 years (January 1, 2009, to December 31, 2014). Included were 24 179 nonpregnant participants with RLS and 145 194 age- and sex-matched participants without RLS at baseline (2006-2008), who were free of suicide, self-harm, cardiovascular disease, or cancer at study baseline. Data analysis was performed from February 1, 2018, to January 1, 2019. <h3>Exposure</h3> Diagnosis of RLS, as identified by the<i>International Classification of Diseases</i>,<i>Ninth Revision</i>code. <h3>Main Outcomes and Measures</h3> Incident suicide and self-harm event, identified by the<i>International Classification of Diseases</i>,<i>Ninth Revision</i>diagnosis code. <h3>Results</h3> Among 169 373 participants in the current analysis, the mean (SD) age was 49.4 (9.1) years; 53 426 (31.5%) participants were men. During a mean (SD) follow-up duration of 5.2 (2.2) years, 119 incident suicide and self-harm cases were identified. Individuals with RLS had a higher risk of suicide or self-harm compared with those without RLS (adjusted hazard ratio, 2.66; 95% CI, 1.70-4.15), after adjusting for lifestyle factors (eg, alcohol and obesity), presence of chronic diseases (eg, depression, insomnia, diabetes, chronic kidney disease, peripheral neuropathy, iron-deficiency anemia, and Parkinson disease), and use of medications. Excluding those with depression, insomnia, obstructive sleep apnea, and other common chronic conditions, the significant association between RLS and suicide or self-harm persisted (adjusted hazard ratio, 4.14; 95% CI, 2.17-7.92). <h3>Conclusions and Relevance</h3> Restless legs syndrome was associated with a high risk of suicide and self-harm, and the risk was independent of most identified diseases and conditions.
Molecular Characterization of Locally Relapsed Head and Neck Cancer after Concomitant Chemoradiotherapy
Authors: Reinout H. de Roest, Steven W. Mes, Jos B. Poell, Arjen Brink, Mark A. van de Wiel, Elisabeth Bloemena, Elena Thai, Tito Poli, C. René Leemans, Ruud H. Brakenhoff
Journal: Clinical Cancer Research (2019)

To investigate the pathobiological origin of local relapse after chemoradiotherapy, we studied genetic relationships of primary tumors (PT) and local relapses (LR) of patients treated with chemoradiotherapy.First, low-coverage whole genome sequencing was performed on DNA from 44 biopsies of resected head and neck squamous cell carcinoma (HNSCC) specimens (median 3 biopsies/tumor) to assess suitability of copy number alterations (CNAs) as biomarker for genetic relationships. CNAs were compared within and between tumors and an algorithm was developed to assess genetic relationships with consideration of intratumor heterogeneity. Next, this CNA-based algorithm was combined with target enrichment sequencing of genes frequently mutated in HNSCC to assess the genetic relationships of paired tumors and LRs of patients treated with chemoradiotherapy.Genetic relationship analysis using CNAs could accurately (96%) predict tumor biopsy pairs as patient-matched or independent. However, subsequent CNA analysis of PTs and LRs after chemoradiotherapy suggested genetic relationships in only 20% of cases, and absence in 80%. Target enrichment sequencing for mutations confirmed absence of any genetic relationship in half of the paired PTs and LRs.There are minor variations in CNA profiles within different areas of HNSCC tumors and many between independent tumors, suggesting that CNA profiles could be exploited as a marker of genetic relationship. Using CNA profiling and mutational analysis of cancer driver genes, relapses after chemoradiotherapy appear to be partially genetically related to the corresponding PTs, but seem often genetically unrelated. This remarkable observation warrants further studies and will impact therapeutic innovations and prognostic modeling when using index tumor characteristics.