tbuckley/cabot-search huggingface dataset:
Prognostic impact of <i>FGFR1</i> amplification in patients with early-stage resected squamous cell carcinomas of the lung (SQCLC).
Authors: Matthew David Hellmann, Lu Wang, Melissa Wynne, Camelia S. Sima, Mark G. Kris, Andre L. Moreira, Natasha Rekhtman, Paul K. Paik
Journal: Journal of Clinical Oncology (2013)

7559 Background: The spectrum and frequency of oncogenes in squamous cell lung cancers (SQCLCs) has recently been defined. Amplification of fibroblast growth factor receptor 1 (FGFR1) occurs in ~20% of SQCLCs; clinical trials of FGFR1 inhibitors for advanced SQCLCs are ongoing. The frequency, clinicopathologic features, and prognosis of FGFR1 amplification in early-stage, resected SQCLCs have been reported but with discrepant results (Kim et al, J Clin Oncol 2012, Heist et al, J Thorac Oncol 2012). Methods: A cohort of histopathologically-defined and clinically-annotated resected SQCLCs was tested for FGFR1 amplification by FISH (Zytovision Dual Color Probe). Amplification was defined by FGFR1 copy number ≥2.2x CEP8 control copy number and was assessed by two evaluators (MW, LW) who were blinded to clinical results. Disease-free survival (DFS) was defined as date of resection until relapse, recurrence, or death, whichever occurred first. We assessed association between FGFR1status and clinical features (Fisher’s exact test) and DFS (long-rank test). Multivariate DFS analysis was performed using Cox regression analysis. Results: 63 resected SQCLCs were evaluated. FGFR1 amplification was detected in 16 (24%). The median age of the cohort was 70 years (range 48-88). 15 (24%) currently smoked, 47 (75%) former, 1 (1%) never. 7 (11%) received neo-adjuvant therapy. 35 (56%) were stage I, 15 (24%) were stage II, and 13 (20%) were stage IIIA. There was no association between FGFR1 amplification and age (p&gt;0.99), sex (p&gt;0.99), smoking status (p=0.32), or stage of disease (p=0.18). 1-year and median DFS in FGFR1-amplified vs non-amplified cases were 86% vs 71% (p=0.022) and not reached vs 2.3 yrs (95% CI 1.1-3.4 yrs), respectively. Multivariate analysis (FGFR1 status, sex, and stage) found FGFR1amplification significantly associated with improved DFS (HR 3.2, 95% CI 1.1-9.4). Conclusions: In this cohort of resected SQCLCs FGFR1 amplification was associated with improved outcomes. There was no association between FGFR1 status and sex, age, smoking status, or stage. FGFR1 amplification is common in SQCLCs.
Epigenetic reprogramming of immune cells in injury, repair, and resolution
Authors: Katarzyna Placek, Joachim L. Schultze, Anna C. Aschenbrenner
Journal: Journal of Clinical Investigation (2019)

Immune cells are pivotal in the reaction to injury, whereupon, under ideal conditions, repair and resolution phases restore homeostasis following initial acute inflammation. Immune cell activation and reprogramming require transcriptional changes that can only be initiated if epigenetic alterations occur. Recently, accelerated deciphering of epigenetic mechanisms has extended knowledge of epigenetic regulation, including long-distance chromatin remodeling, DNA methylation, posttranslational histone modifications, and involvement of small and long noncoding RNAs. Epigenetic changes have been linked to aspects of immune cell development, activation, and differentiation. Furthermore, genome-wide epigenetic landscapes have been established for some immune cells, including tissue-resident macrophages, and blood-derived cells including T cells. The epigenetic mechanisms underlying developmental steps from hematopoietic stem cells to fully differentiated immune cells led to development of epigenetic technologies and insights into general rules of epigenetic regulation. Compared with more advanced research areas, epigenetic reprogramming of immune cells in injury remains in its infancy. While the early epigenetic mechanisms supporting activation of the immune response to injury have been studied, less is known about resolution and repair phases and cell type-specific changes. We review prominent recent findings concerning injury-mediated epigenetic reprogramming, particularly in stroke and myocardial infarction. Lastly, we illustrate how single-cell technologies will be crucial to understanding epigenetic reprogramming in the complex sequential processes following injury.
Reply
Authors: Xiu‐Ping Zhang, Yu‐Zhen Gao, Zhen‐Hua Chen, Shu‐Qun Cheng
Journal: Hepatology (2019)

Potential conflict of interest: Nothing to report. We appreciate the letter from Dr. Luo and colleagues in response to our recent report on an Eastern Hepatobiliary Surgery Hospital/Portal Vein Tumor Thrombus (EHBH/PVTT) scoring system to aid in decision making on hepatectomy for hepatocellular carcinoma (HCC) patients with PVTT. We would like to thank the readers for their interest in our study. In the letter, Luo et al. expressed concern that overall survival (OS) was set as the primary study endpoint; they believe disease‐free survival (DFS) was more important than OS. However, DFS was not more accurate than OS because the diagnosis of HCC recurrence is based on timely regular surveillance. When recurrent HCC was diagnosed, the patients were actively treated with radiofrequency ablation, percutaneous ethanol injection, transarterial chemoembolization (TACE), or repeat liver resection (LR), depending on the general condition of the patient, the underlying liver functional status, the number and location of HCC recurrence, the patients' requests, and the results of discussion with our multidisciplinary team. Because the study is not a randomized controlled trial (RCT) in nature, differences in anti‐recurrence therapy of HCC among groups was unavoidable and foreseen. Although the other effective treatments for HCC recurrence may influence the prognosis of HCC patients, the EHBH/PVTT score also showed a good ability to distinguish DFS in HCC patients with PVTT (Supporting Table S6; Supporting Figs. S7‐S12). Furthermore, some patients in this study received postoperative TACE. Recent reports also showed postoperative TACE improved the OS of HCC patients with macrovascular invasion after negative‐margin (R0) LR.1 There were no significant differences in patients under postoperative TACE between the EHBH/PVTT score ≤3 group and the EHBH/PVTT score >3 group (42.8% versus 35.6%; P = 0.167). Whether postoperative TACE or preoperative antiviral treatment was beneficial to HCC patients with PVTT should be studied further in multicenter RCTs. In addition, alpha‐fetoprotein ≥20 ng/mL = 2 was based on regression coefficients (B) of the multivariate Cox regression model instead of artificial setting. Finally, this EHBH/PVTT score requires validation from study groups, with hepatitis C virus infection or alcoholism or nonalcoholism being the prevailing etiologies of HCC in Western countries. This will be our next step. Liver surgeons should not shy away from LR for selected PVTT patients. It is imperative to design multicenter RCTs to assess LR in some selected PVTT patients.
Stereotactic radiosurgery for patients with recurrent head and neck carcinoma: Five years’ observation report.
Authors: Koji Kawaguchi
Journal: Journal of Clinical Oncology (2012)

e16049 Background: The aim of this study is to examine the effect of stereotactic radiosurgery (SRS) in the treatment of advanced, recurrent lesions for head and neck carcinoma both with and without lymph node involvement. Methods: Between April 2006 and July 2007, 22 patients (mean age 67 years) with advanced, recurrent head and neck carcinoma were treated with SRS by CyberKnife-II. All of the patients excepted one had biopsy confirmed disease prior to SRS. Patients included 3 rT2, 8 rT3, and 9 rT4; 8 of the patients had lymph node metastases. Marginal SRS doses were 20-42 Gy delivered in two to five fractions. Starting one month after SRS, all patients received S-1 oral chemotherapy for one year. Results: At an overall median follow-up of 64 months (range, 4-69 months), for the 14 locally recurrent patients without lymph node metastases, 9 patients (64.3%) had a complete response (CR), 1 patient (7.1%) had a partial response (PR), 1 patient (7.1%) had stable disease (SD), and 3 patients (21.4%) had progressive disease (PD). For the 8 patients with lymph node metastases, 1 patient with a single retropharyngeal (12.5%) had CR; the remaining 7 patients (87.5%) all progressed. Nine patients have died from their cancer. The overall 5-year survival for the patients with and without lymph node metastases was 12.5% and 78.6%, respectively. Conclusions: These results show the benefit of stereotactic radiosurgery salvage treatment for advanced, recurrent lesions, without lymph node metastases in previously irradiated head and neck cancer.
A psychosocial and pshycoeducational intervention for cancer patients integrated into routine care: A study from India.
Authors: Anita Chandra
Journal: Journal of Clinical Oncology (2012)

e19518 Background: Patients with cancer experience significant distress and access to effective psychosocial care is limited by lack of systematic approach. This paper presents results of a study to evaluate the effectiveness of a brief tailored psychosocial intervention delivered by health professionals in cancer care in developing countries. Methods: Health professionals deliver the multicomponent, psychoeducational and psychosocial intervention focusing on core concepts of quality of life, supportive-expressive, cognitive, social functioning, symptom scale and dignity-conserving care. A total of 100 patients recruited across all tumour sites, from July 2011 to December 2011, in a University Hospital in India. Eligible patients received 2 sessions, each for 30 minutes in length, delivered face-to-face at baseline and 12 week follow-up. Results: Quality of life was measured by using the European Organisation for Research and Treatment of Cancer (EORTC) QLQ-C30 questionnaire .In this study the functional scales were high, whereas in the symptom scales fatigue (48.9%) and financial difficulties (45.53%) were noted. Percentages of families who evaluated by the palliative care team voted as useful or very useful were: 80% (symptom control), 85% (emotional support), 86% (family support), and 87% (care coordination). Compared with participants receiving usual oncology care, those receiving a palliative care-focused intervention addressing psychosocial care provided concurrently with oncology care had higher scores for quality of life and mood. Conclusions: This study will provide important information about the effectiveness of a brief tailored psychological intervention for patients with cancer in a developing country. This model of care should be a systematic implementation in routine clinical practice cancer settings in resource restraints countries. [Table: see text]
Case 23-2019: A 52-Year-Old Man with Fever, Cough, and Hypoxemia
Authors: Charles C. Hardin, Rajeev Malhotra, Milena Petranović, Sheila Klassen, Nino Mihatov, Derek H. Oakley
Journal: New England Journal of Medicine (2019)

A 52-year-old man presented to the hospital for evaluation and treatment of hypoxemia. Seven days before presentation, nonproductive cough and a temperature of 38.2°C developed. A chest radiograph showed markedly asymmetric lung opacities. Diagnostic tests were performed.
The Conundrum of the United States Medical Licensing Examination Score Reporting Structure
Authors: Jennifer L. Swails, Omowunmi Aibana, Barbara J. Stoll
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 Podcasts Clinical Reviews Editors' Summary Medical News Author Interviews More 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 journal
Screening for Hepatitis B in Pregnant Women
Authors: Jill Jin
Journal: JAMA (2019)

US Preventive Services Task Force; Douglas K. Owens, MD, MS; Karina W. Davidson, PhD, MASc; Alex H. Krist, MD, MPH; Michael J. Barry, MD; Michael Cabana, MD, MA, MPH; Aaron B. Caughey, MD, PhD; Chyke A. Doubeni, MD, MPH; John W. Epling Jr, MD, MSEd; Alex R. Kemper, MD, MPH, MS; Martha Kubik, PhD, RN; C. Seth Landefeld, MD; Carol M. Mangione, MD, MSPH; Lori Pbert, PhD; Michael Silverstein, MD, MPH; Melissa A. Simon, MD, MPH; Chien-Wen Tseng, MD, MPH, MSEE; John B. Wong, MD
Abstract P073: Primary Healthcare Providers’ Attitudes and Counseling Behaviors Related to Dietary Sodium Reduction, DocStyles 2015
Authors: Zerleen S Quader, Mary E Cogswell, Sallyann C King, Robert K Merritt, Jing Fang
Journal: Circulation (2016)

Introduction: Hypertension is the most common diagnosis given by primary care physicians in the United States. Reductions in blood pressure can be achieved through lifestyle modifications, such as dietary sodium reduction. Previous studies indicate most adults in the United States who receive advice from their physician or health care provider to reduce their sodium take action, but only 13%-25% of all adults and 30%-60% of hypertensive adults report receiving advice. Hypothesis: We hypothesized the majority of providers would report advising patients with hypertension to reduce their sodium intake and agree that most of their patients should reduce their sodium intake. Methods: DocStyles is a national web-based survey of health care providers. In 2015, 465 family/general practitioners, 535 internists, and 251 nurse practitioners were asked questions about their practices related to sodium intake. Results: A majority of providers agreed or strongly agreed with the statement, most of my patients should reduce their sodium intake (78%) and reported advising hypertensive patients (84%), pre-hypertensive patients (69%), and chronic kidney disease patients (71%) to “consume less salt.” Overall fewer providers reported advising diabetic patients (48%) and African-American patients (43%) to consume less salt. However, responses varied significantly by provider type. More than 50% of internists and nurse practitioners reported advising diabetic patients and 51% of nurse practitioners reported advising African-American patients to consume less salt. In addition, 41% of nurse practitioners reported advising all adults to consume less salt compared with 31% of family and general practitioners and 27% of internists. The most commonly reported advice given to patients to consume less salt was to eat less processed food (78%) and to read nutrition labels for sodium content (75%). A majority of providers reported their biggest barrier to reducing dietary sodium intake with hypertensive and pre-hypertensive patients was that “patients are unlikely to comply” (62%). The next most commonly reported barriers were “patients have more immediate health issues” (21%) and “lack of resources for patient education” (19%). Eighteen percent reported “no major barriers”, 14% reported lack of time, and 8% reported “not enough scientific evidence.” Conclusion: Most providers agree their patients should reduce their sodium intake and advise patients with hypertension, pre-hypertension, and chronic kidney disease to reduce their intake. Advice was less likely to be reported for African-American and diabetic patients, who also are at high risk of cardiovascular disease. In conclusion, further effort and educational resources may be required to enable providers to effectively counsel their patients about salt reduction.
Yoga for Anxiety and Depression Associated With Parkinson Disease
Authors: Anita Slomski
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
Reply to Chen Cheng, Sunxiang Ma, and Yang Liu’s Letter to the Editor re: Dan Wood, Andrew Baird, Luca Carmignani, et al. Lifelong Congenital Urology: The Challenges for Patients and Surgeons. Eur Urol 2019;75:1001–7
Authors: Dan Wood, Andrew Baird, Luca Carmignani, Gunter De Win, Piet Hoebeke, Gundela Holmdahl, Gianantonio Manzoni, Rien J.M. Nijman, Claire Taylor, Serdar Tekgul
Journal: European Urology (2019)
Resistance to BRAF inhibition in melanoma: An epigenetic approach.
Authors: Steve Walston, Nicolaus Gordon, Arnab Chakravarti, Kamalakannan Palanichamy
Journal: Journal of Clinical Oncology (2012)

e19040 Background: Melanoma only accounts for 4% of skin cancer while causing 75% of cancer related deaths. Worldwide incidence is increasing faster than any other cancer, and there are few effective treatment options for invasive disease translating to poor survival. The burgeoning understanding of molecular mechanisms driving carcinogenesis creates unique opportunities to develop targeted therapy. This is especially apparent in the case of BRAF in melanoma. BRAF V600E mutations occur in up to 50% of melanomas endowing these tumors with a constitutively activated MAPK pathway. Blockade of BRAF mutated tumors shows impressive initial responses above 80%. However, single-agent targeted therapy is often plagued with an emergence of resistant clones, and these impressive responses were transient. Diverse resistance mechanisms have been reported at the transcriptome level in patients treated with BRAF inhibitors. However, reports elucidating the prominent epigenetic regulators of resistance to BRAF inhibition are lacking. Methods: We sequenced the DNA of 14 melanoma cell lines and determined 9 had BRAF V600E mutation and 5 were wild type. We also sequenced cancer genes such as p53, PTEN, cKit, NRAS, etc. The BRAF mutant cells were exposed to PLX4032 (BRAF V600E inhibitor) and the concentrations were incrementally increased to develop resistant clones. This resistance was corroborated using annexin V / PI assay to display approximately a 50% decrease in apoptosis in drug resistant cells compared with control cells after 5 days of 5 µM PLX4032 exposure. The epigenome was profiled in control and resistance clones. Results: The statistically significant clusters were identified and currently we are validating their relevance using functional models. We are also profiling the epigene expression levels in melanoma patient biopsies to determine their predictive and prognostic value. Conclusions: It is likely the epigenome plays an integral role in the previously demonstrated mechanisms of BRAF resistance. Our study should illuminate connections with pathways conveying drug resistance to increase understanding of these mechanisms. Consequently, it may be possible to develop improved treatments and prognostic biomarkers.
Phase II trial of ifosfamide in combination with sorafenib in patients with advanced soft tissue sarcoma: A Spanish Group for Research on Sarcomas (GEIS) study.
Authors: Xavier Garcia del Muro, Joan Maurel, Javier Martinez Trufero, Javier Lavernia, Antonio Lopez-Pousa, Ramon De Las Penas, Ricardo Cubedo, Joaquin Fra, Antonio Casado, Ana De Juan, Laura Jimenez Colomo, Javier Martin Broto
Journal: Journal of Clinical Oncology (2013)

10523 Background: Recent studies suggest that VEGFR inhibition could play a role in the treatment of soft tissue sarcoma (STS). Prior studies by our group showed that the combination of ifosfamide with sorafenib resulted in preclinical additive activity and that was feasible and safe in the phase I trial. Methods: Patients (pts) with advanced STS, previously treated with doxorubicin, no prior ifosfamide, ECOG PS 0-2, and adequate hematological, renal and hepatic function, were enrolled in this multicenter phase II study, receiving sorafenib 400 mg bid po continuously and ifosfamide 2 g/m2 iv for 3 days together with mesna 400 mg/m2 every 3 weeks. The primary endpoint was progression-free rate (PFR) at 3 months. A one-sample binomial design was used (PFR P0=40%, P1=60%, α=0.10, β=0.20), requiring at least 19 of 35 pts free of progression at 3 months to be considered positive. Results: From September 09 to March 12, 35 pts were enrolled at 11 centers. Median age was 55 (18-73). PS: 0-13, 1-18; 2-4 pts. Histologic types were: LMS 12, Lipo 6, SS 5, MPNST 2, other 10 pts. . The median number of cycles administered per patient was 4. PFR at 3 months was 67%, with 23 pts being free of progression at 3 months. Median progression-free survival was 4.8 months (95% CI, 1.9-6.3) and median overall survival was 16.2 months. PR was achieved in 17% pts. Most common grade 3-4 toxicities were asthenia (25%), hand-foot syndrome (11%) and neutropenia (20%) resulting in 3 episodes of neutropenic fever. Other common toxicities (G1-4) included emesis (34%), rash (22%), diarrhea (34%), hypertension (11%) and mucositis (9%). Conclusions: The combination of ifosfamide and sorafenib is active and has acceptable toxicity in pts with doxorubicin pretreated STS. The PFR at 3 months might exceed the expected with ifosfamide alone warranting further investigation. Clinical trial information: EudraCT: 2007-002176-34.