tbuckley/cabot-search huggingface dataset:
Cardiovascular disease risk in survivors of 20 adult cancers.
Authors: Helen Strongman, Sarah Gadd, Anthony Matthews, Kathryn Mansfield, Susannah Jane Stanway, Alexander R. Lyon, Isabel dos-Santos-Silva, Liam Smeeth, Krishnan Bhaskaran
Journal: Journal of Clinical Oncology (2019)

11571 Background: There are concerns about long-term cardiovascular disease (CVD) risk in cancer survivors, but few studies have quantified the risks for a wide range of cancers and specific CVD outcomes. Methods: Using UK electronic health records, we identified cohorts of adults alive one year after a cancer diagnosis at 20 different sites. Risks of a range of CVD outcomes were compared to age, sex and general practice matched cancer free controls using Cox regression; crude and adjusted models were compared to investigate the role of shared cancer/CVD risk factors (e.g. smoking and diabetes). Results: 126 120 cancer survivors and 603 144 controls were followed over a median (IQR) 4.6 (2.5-8.1) and 5.6 (3.2-9.2) years. Crude and adjusted hazard ratios (HRs) were similar. In adjusted models, there was strong evidence (p&lt;0.01) of increased risk of CVDs among cancer survivors compared with controls: venous thromboembolism (VTE, 18 cancers), heart failure/cardiomyopathy (7 cancers), arrhythmia (4 cancers), and stroke (3 cancers). In stratified analyses HRs were higher in younger people and continued beyond 5 years post diagnosis. Conclusions: We found increased long term CVD risk among survivors of several cancers compared to the general population, which varied by cancer site and specific CVD outcome.[Table: see text]
Prediction of treatment (tx)-induced fatigue in breast cancer (BC) patients (pts) using machine learning on genome-wide association (GWAS) data in the prospective CANTO cohort.
Authors: Sangkyu Lee, Joseph O. Deasy, Jung Hun Oh, Antonio Di Meglio, Sandrine Boyault, Marina Rousseau-Tsangaris, Celine Besse, Emilie Thomas, Anne Boland-Augé, Paul H. Cottu, Olivier Tredan, Christelle Levy, Anne-Laure Martin, Sibille Everhard, Patricia A. Ganz, Ann H. Partridge, Stefan Michiels, Jean-Francois Deleuze, Fabrice Andre, Ines Maria Vaz Duarte Luis
Journal: Journal of Clinical Oncology (2019)

11515 Background: Many BC survivors report fatigue. The relevant genomic correlates of fatigue after BC are not well understood. We applied a previously validated machine learning methodology (Oh 2017) to GWAS data to identify biological correlates of fatigue induced after tx. Methods: We analyzed 3825 BC pts with GWAS data (Illumina InfiniumExome24 v 1.1) from the CANTO study (NCT01993498). The outcome of this study was post-tx fatigue 1 year after the end of primary chemotherapy/radiotherapy/surgery using the EORTC C30 fatigue subscale (overall fatigue) and the EORTC FA 12 fatigue domains (physical/emotional/cognitive). For each domain, we limited the study group to those with zero baseline fatigue and defined severe fatigue change as score increase above the third quartile. We tested univariate correlations between severe fatigue in each domain and 496539 SNPs as well as relevant clinical variables. The machine learning prediction model based on preconditioning random forest regression (PRFR) (Oh et al., 2017), was then built using the SNPs with ancestry adjusted univariate p-value &lt; 0.001 and clinical variables with Bonferroni adjusted p-value &lt; 0.05. The model was validated in a holdout subset of the cohort. Gene set enrichment analysis (GSEA) was performed using MetaCore to identify key biological correlates relevant to tx-induced fatigue. Results: Distinct results were found by fatigue domain (table). GSEA showed that the cognitive fatigue model SNPs included biomarkers for cognitive disorders (p = 1.6 x 10 -12 ) and glutamatergic synaptic transmission (p = 1.6 x 10 -8 ). Conclusions: A SNP based model had differential performance by fatigue domain, with a potential genetic role on risk and biology for tx induced cognitive fatigue. Further research to explore biomarkers of tx induced fatigue are needed. [Table: see text]
JACC: CardioOncology: Poised to Serve a Maturing, Collaborative Field
Authors: Bonnie Ky, MD, MSCE, FACC
Journal: JACC CardioOncology (2019)

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I first became interested in the field of cardio-oncology as a young cardiology fellow. I was fascinated by mechanisms of cardiovascular disease. With the guidance of wonderful mentors, I was driven to understand further how perturbation of fundamental signaling pathways were
US supermarket chain Walmart limits gun and ammunition sales
Authors: Janice Hopkins Tanne
Journal: BMJ (2019)

Walmart, the world’s largest retailer with more than 5000 stores in the US, announced on 4 September that it was no longer selling hand guns and military style rifles and would end the sale of ammunition for handguns and for the military style weapons used in mass shootings.

It said it would ask customers not to openly carry guns in its stores, even in states where this is permitted, unless they are police officers.1

Customers will still be able to carry concealed weapons in states where this is allowed if they have a permit.

Walmart chief executive …
OS12.4 In vivo dynamics and targeting of vessel co-option in glioma
Authors: G Seano, A Griveau, S Shelton, S Krishnan, N Wang, J Kloepper, E Huillard, T Batchelor, A Stemmer-Rachamimov, M Aghi, R Jain, D Rowitch
Journal: Neuro-Oncology (2019)

Abstract BACKGROUND Gliomas comprise heterogeneous malignant glial and stromal cells. While blood vessel co-option is a potential mechanism to escape anti-angiogenic therapy, the relevance of glial phenotype in this process is unclear. MATERIAL AND METHODS Here, we intravitally study preclinical syngenetic models of glioma as well as patient-derived cells transplanted orthotopically. Moreover, we profoundly confirm our preclinical results with histological studies on patient specimens. RESULTS We show that Olig2+ oligodendrocyte precursor-like glioma cells invade by single-cell vessel co-option and preserve the blood-brain barrier (BBB). Conversely, Olig2-negative glioma cells form dense perivascular collections and promote angiogenesis and BBB breakdown, leading to innate immune cell activation. Experimentally, Olig2 promotes Wnt7b expression, a finding that correlates in human glioma profiling. Targeted Wnt7a/7b deletion or pharmacologic Wnt inhibition blocks Olig2+ glioma single-cell vessel co-option and enhances responses to temozolomide. Finally, Olig2 and Wnt7 become upregulated after anti-VEGF treatment in preclinical models and patients. CONCLUSION Here, we show that glioma is able to employ vessel co-option, i.e. the movement of tumor cells towards and along the pre-existing vasculature. Glioma oligodendrocyte-like (OPCL) cells express Wnt7 that is necessary for vessel co-option and Wnt inhibitors significantly improve survival with temozolomide. Moreover, we demonstrated that anti-VEGF-treatment of glioma selects for Olig2/Wnt7+ cells
Comprehensive genomic profiling of patients with favorable prognosis in osteosarcoma.
Authors: Weifeng Liu, Zhen Huang, Yi Ding, Yongkun Yang, Tao Jin, Zhiping Deng, Hairong Xu, Xuan Wang, Yanrui Zhang, Huina Wang, Feng Lou, Shanbo Cao, Xiaohui Niu
Journal: Journal of Clinical Oncology (2019)

e22501 Background: Osteosarcoma (OS) is characterized by complex genetic features and mysterious biological behavior. Genomic technologies are starting to give more insights. However, recent investigations have focused on patients with the advanced or metastatic disease. This study intended to evaluate the genetic landscape and identify new prognostic biomarkers in OS pts with good prognosis. Methods: This study conducted in-depth genomic profiling in a cohort of 21 patients (MSTS stage II) with long-term follow-up. Whole exome sequencing of primary tumors with matched normal tissues were performed. Sequencing data were analyzed to call tumor specific single nucleotide variants (SNV), small insertions and deletions (Indels), copy number variations (CNV) and chromosomal rearrangements and their prevalence was compared to the pts with metastatic disease reported before (Wang et al, 2018). Tumor mutation burden (TMB) and microsatellite instability (MSI) was analyzed, with additional analysis for mutational signatures. The endpoint was disease free survival (DFS). Results: 21 participants were enrolled between July. 23th, 2008 and Aug. 19th, 2013. 21 pts (M/F 13/8), median age 17y (5-33). Median DFS was 88.4 (95% CI 61.27–111.77) months. The top ranked altered genes were MUC4 (67%), FRG1 (62%), TXNDC2 (62%), ZNF717 (62%), ANKRD20A4 (57%), IGSF3 (52%), MUC16 (52%), NBPF10 (52%), MUC12 (48%) and ARID1A (43%). TMB was evaluated as lower level with a median value of 1.11 muts/MB (range from 0.78 to 3.58), relative to the other solid tumors. None pathogenic and likely pathogenic germline mutations were detected. Mutation signature 5 and 6 were most prevalent. CNV were frequently happened in stage II OS with an incidence of 80.9% (17/21). Among these, The co-occurrence of copy number gain (CNG) and copy number loss (CNL) significantly correlated with DFS (p = 0.0164), comparing with pts of either CNG or CNL . While CNV of driver genes in stage II OS were different from those of stage III published before (Wang et al, 2018), TP53 (0% vs 30% ), RB1 (4.5% vs 60%), CDKN2A (0% vs 30% ), MYC (0% vs 60%) and MDM2 (0% vs 60%). Conclusions: Stage II OS with favorable prognosis has unique genetic characterizes relative to metastatic OS. This study indicates that MUC family could be one of prognostic indicators. Genes with CNV, and the state which CNV occurs could provide clinical significance for the discovery of prognostic markers, which need to be validated by prospective prognostic data.
Proposals to Redesign Medicare Part D — Easing the Burden of Rising Drug Prices
Authors: Stacie B. Dusetzina, Nancy L. Keating, Haiden A. Huskamp
Journal: New England Journal of Medicine (2019)

Interview with Dr. Stacie Dusetzina on three proposals for redesigning the Medicare Part D prescription-drug benefit. (09:54)Download Amid concerns about high drug prices, policymakers are considering options for modifying the Medicare Part D prescription-drug benefit to reduce spending by beneficiaries and taxpayers. The redesigns being considered shift spending and benefit phases in various ways.
Combination of PPARγ Agonist Pioglitazone and Trabectedin Induce Adipocyte Differentiation to Overcome Trabectedin Resistance in Myxoid Liposarcomas
Authors: Roberta Frapolli, Ezia Bello, Marianna Ponzo, Ilaria Craparotta, Laura Mannarino, Sara Ballabio, Sergio Marchini, Laura Carrassa, Paolo Ubezio, Luca Porcu, Silvia Brich, Roberta Sanfilippo, Paolo Giovanni Casali, Alessandro Gronchi, Silvana Pilotti, Maurizio D'Incalci
Journal: Clinical Cancer Research (2019)

Abstract Purpose: This study was aimed at investigating whether the PPARγ agonist pioglitazone—given in combination with trabectedin—is able to reactivate adipocytic differentiation in myxoid liposarcoma (MLS) patient-derived xenografts, overcoming resistance to trabectedin. Experimental Design: The antitumor and biological effects of trabectedin, pioglitazone, and the combination of the two drugs were investigated in nude mice bearing well-characterized MLS xenografts representative of innate or acquired resistance against trabectedin. Pioglitazone and trabectedin were given by daily oral and weekly i.v. administrations, respectively. Molecular studies were performed by using microarrays approach, real-time PCR, and Western blotting. Results: We found that the resistance of MLS against trabectedin is associated with the lack of activation of adipogenesis. The PPARγ agonist pioglitazone reactivated adipogenesis, assessed by histologic and gene pathway analyses. Pioglitazone was well tolerated and did not increase the toxicity of trabectedin. The ability of pioglitazone to reactivate adipocytic differentiation was observed by morphologic examination, and it is consistent with the increased expression of genes such as ADIPOQ implicated in the adipogenesis process. The determination of adiponectin by Western blotting constitutes a good and reliable biomarker related to MLS adipocytic differentiation. Conclusions: The finding that the combination of pioglitazone and trabectedin induces terminal adipocytic differentiation of some MLSs with the complete pathologic response and cure of tumor-bearing mice provides a strong rationale to test the combination of trabectedin and pioglitazone in patients with MLS.
Clonal Mutations Activate the NF-κB Pathway to Promote Recurrence of Nasopharyngeal Carcinoma
Authors: Rui You, You-Ping Liu, De-Chen Lin, Qing Li, Tao Yu, Xiong Zou, Mei Lin, Xiao-Long Zhang, Gui-Ping He, Qi Yang, Yi-Nuan Zhang, Yu-Long Xie, Rou Jiang, Chen-Yan Wu, Chao Zhang, Cheng Cui, Jing-Qi Wang, Yue Wang, Ai-Hua Zhuang, Gui-Fang Guo, Yi-Jun Hua, Rui Sun, Jing-Ping Yun, Zhi-Xiang Zuo, Ze-Xian Liu, Xiao-Feng Zhu, Tie-Bang Kang, Chao-Nan Qian, Hai-Qiang Mai, Ying Sun, Mu-Sheng Zeng, Lin Feng, Yi-Xin Zeng, Ming-Yuan Chen
Journal: Cancer Research (2019)

Abstract The genetic events occurring in recurrent nasopharyngeal carcinoma (rNPC) are poorly understood. Here, we performed whole-genome and whole-exome sequencing in 55 patients with rNPC and 44 primarily diagnosed NPC (pNPC), with 7 patients having paired rNPC and pNPC samples. Previously published pNPC exome data were integrated for analysis. rNPC and pNPC tissues had similar mutational burdens, however, the number of clonal mutations was increased in rNPC samples. TP53 and three NF-κB pathway components (TRAF3, CYLD, and NFKBIA) were significantly mutated in both pNPC and rNPC. Notably, mutations in TRAF3, CYLD, and NFKBIA were all clonal in rNPC, however, 55.6% to 57.9% of them were clonal in pNPC. In general, the number of clonal mutations in NF-κB pathway–associated genes was significantly higher in rNPC than in pNPC. The NF-κB mutational clonality was selected and/or enriched during NPC recurrence. The amount of NF-κB translocated to the nucleus in samples with clonal NF-κB mutants was significantly higher than that in samples with subclonal NF-κB mutants. Moreover, the nuclear abundance of NF-κB protein was significantly greater in pNPC samples with locoregional relapse than in those without relapse. Furthermore, high nuclear NF-κB levels were an independent negative prognostic marker for locoregional relapse-free survival in pNPC. Finally, inhibition of NF-κB enhanced both radiosensitivity and chemosensitivity in vitro and in vivo. In conclusion, NF-κB pathway activation by clonal mutations plays an important role in promoting the recurrence of NPC. Moreover, nuclear accumulation of NF-κB is a prominent biomarker for predicting locoregional relapse-free survival. Significance: This study uncovers genetic events that promote the progression and recurrence of nasopharyngeal carcinoma and has potential prognostic and therapeutic implications. See related commentary by Sehgal and Barbie, p. 5915
Abstract 17353: Lower Income and Worse Clinical Outcomes: An Empirical Study in the State of New Jersey
Authors: Georgia Barbayannis, Davit Sargsyan, I-Ming Chiu, William J Kostis, Noah Michel, Javier Cabrera, Nora M Cosgrove, John B Kostis
Journal: Circulation (2017)

Introduction: A patient’s socioeconomic status (SES) plays a vital role in clinical outcomes. Analyzing the impact of an individual’s SES on health outcomes is often challenging since the SES measu...
Commentary on: Endoscopic vein harvesting for coronary artery bypass grafting in the UK: what we believe and what we do. A Commentary on the article “Use of endoscopic vein harvesting (EVH) during coronary artery bypass grafting in United Kingdom: The EVH survey”, Int J Surg 2019;69:146-151
Authors: Irbaz Hameed, Ajita Naik, Mario Gaudino
Journal: International Journal of Surgery (2019)
A Case of Progressive Myelopathy in a Middle-aged Woman
Authors: Alexandra Muccilli, Romain Cayrol, Kathryn A. Kvam
Journal: JAMA Neurology (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 Neurology 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 Neurology journal
Less burn, more fat: electronic cigarettes and pulmonary lipid homeostasis
Authors: Aran Singanayagam, Robert J. Snelgrove
Journal: Journal of Clinical Investigation (2019)

Electronic nicotine delivery systems (ENDS) are rapidly increasing in popularity due to the perception that they may represent a safe alternative to conventional cigarettes. However, a growing body of evidence indicates that ENDS exposure can disrupt maintenance of pulmonary immune homeostasis and antimicrobial immunity. In this issue of the JCI, Madison et al. demonstrate that in mice, chronic ENDS exposure induces profound alterations in lipid homeostasis. ENDS-exposed mice showed irregularities in the surfactant-secreting lamellar bodies within type 2 alveolar cells and increased intracellular phospholipid accumulation within alveolar macrophages. Moreover, ENDS-exposed mice displayed greater inflammation and tissue damage in response to influenza A, which may be due to downregulated expression of a viral pattern-recognition receptor in alveolar macrophages. Collectively, the results of this study identify previously unrecognized adverse effects of ENDS exposure on pulmonary lipid metabolism, although the implication of these effects on long-term respiratory health requires future exploration.
Using hospital claims data to identify ovarian cancer recurrence: A validation study.
Authors: Jennifer C. Livaudais, Natalia Egorova, Monica Prasad Hayes, Elizabeth A. Howell, Juan P. Wisnivesky, Rebeca Franco, Nina Bickell
Journal: Journal of Clinical Oncology (2012)

e15513 Background: The use of administrative hospital claims data in research studies offers a promising alternative to conducting expensive chart abstraction to assess utilization and health outcomes. However, the validity of using claims data to capture ovarian cancer recurrence is unknown. Methods: We used two strategies to identify recurrent ovarian cancer: 1) a previously validated algorithm of secondary malignancy diagnosis codes used to identify recurrent breast cancer, adapted to ovarian cancer and 2) a new algorithm we created based on the timing and utilization of secondary chemotherapy or secondary debulking surgery for ovarian cancer. To identify secondary debulking surgery, which does not have its own billing code, weobtained codes used by gynecologic oncology billers from across the nation to identify these procedures. We identified all ovarian cancer patients who had undergone primary debulking surgery followed by initiation of primary chemotherapy at a single academic medical institution in NYC, between 2003 and 2010. We then ran the two recurrence algorithms on this population and randomly selected a sample of 50 patients to assess the sensitivity and specificity of each algorithm versus gold-standard chart abstraction data. Results: When applied to our sample of ovarian cancer patients, the sensitivity of the previously validated algorithm was 91% (95% CI: 57% to 99%), the specificity was 28% (95% CI 16% to 45%), the PPV was 26% (95% CI: 14% to 43%) and the NPV was 92% (95% CI: 66% to 99%). In contrast, the sensitivity of our newly developed algorithm to detect ovarian cancer recurrence based on hospital claims data was 100% (95% CI: 68% to 100%), the specificity was 87% (95% CI: 72% to 95%), the PPV was 69% (95% CI: 41% to 88%) and the NPV was 100% (95% CI: 87% to 100%). Conclusions: An algorithm culled from billers and clinical experts identifying timing and utilization of procedures measured ovarian cancer recurrence with a greater degree of accuracy than a previously validated algorithm to detect cancer recurrence. When complex chart reviews are not feasible, our claims-based algorithm can be used by researchers to answer important questions about ovarian cancer treatment effectiveness.
Use of cardioprotective dexrazoxane and myelotoxicity in anthracycline-treated soft tissue sarcoma patients.
Authors: Marianna Silletta, Mariella Spalato Ceruso, Andrea Napolitano, Alessandro Mazzocca, Sergio Valeri, Luca Improta, Daniele Santini, Giuseppe Tonini, Bruno Vincenzi
Journal: Journal of Clinical Oncology (2019)

11053 Background: Dexrazoxane (DEX) is indicated as a cardioprotective agent for patients receiving doxorubicin, who are at increased risk for cardiotoxicity. Concerns have been raised on the use of DEX, particularly in the adjuvant setting, because of the risk of interference with the antitumor effect of doxorubicin. Two meta-analyses in metastatic breast cancer have rejected this hypothesis, but have shown an apparent increase in the severity of myelosuppression when DEX is used. No data in soft-tissue sarcoma (STS) patients is available, so far. Here, we retrospectively analyzed a cohort of our Institute database to assess whether the addition of DEX causes more bone marrow suppression in STS patients receiving Anthracycline-Ifosfamide (AI) combination in perioperative and advanced setting. Methods: 133 patients who received AI between January 2006 and December 2017 were included. 46 of them received DEX concurrently with the AI treatment. Hospital records were reviewed and available for all patients (the accessibility of all the data was an inclusion criterion). Compared to the non-DEX group, patients who received DEX were more frequently treated in the context of a perioperative setting (respectively 27.3 vs 38.8%). No other differences in terms basal patient features were recorded. Significantly, all patients received similar post-medication after each cycle. Results: Compared with the non-DEX group, DEX treatment was associated with significantly higher rates of G3/4 hematological side effects: leucopenia (28.7 vs 56.5%, p value=0.0014); neutropenia (35.6 vs 69.6%, p value=0.0002); anemia (28.7 vs 41.3%, p value=0.1758); thrombocytopenia (32.1 vs 54.3%, p value=0.0159). Similarly, compared to the non-DEX group, there were more hospitalizations for febrile neutropenia (37.9 vs 63.0%, p value=0.0066) and dose reductions (19.5 vs 39.1%, p value=0.0221) in the DEX group, above all in perioperative setting (15.6 vs 58.3%, p value=0.0085); but no significant difference in the incidence of treatment delays or interruption. Conclusions: Adding DEX to Anthracycline-based chemotherapy in soft-tissue sarcoma patients leads to higher rates of bone marrow suppression in all blood components, as well as more febrile neutropenia events, and dose reductions.