tbuckley/cabot-search huggingface dataset:
Abstract 12505: Prognostic Significance of Myocardial Extracellular Volume Fraction
Authors: Eric Y Yang, Mohammad Ghosn, Mohammad A Khan, Nickalaus L Gramze, Grant W Pickett, Stephen J Pickett, Patrick W Green, Gerd Brunner, Faisal Nabi, Wenyaw Chan, Vijay Nambi, Christie M Ballantyne, Dipan J Shah
Journal: Circulation (2016)

Background: Cardiac magnetic resonance (CMR) techniques permit quantification of cardiac extracellular volume fraction (ECV), inclusive of interstitial fibrosis. ECV and late gadolinium enhancement (LGE), suggestive of cardiac replacement fibrosis, have been independently linked with heart failure (HF) events. Non-coronary artery disease type LGE has not been excluded in ECV measures. We examined associations between ECV censored for LGE-involved segments, LGE presence, and HF events. Methods: Mid short axis T1 maps were divided into 6 cardiac segments, each classified as LGE absent or present. Global ECV was derived from T1 maps using the area-weighted average of only LGE-absent segments. ECV was considered elevated if measured &gt;30%, the upper 95% bounds of a healthy group without known cardiac disease (n=28). Patients were divided into 4 groups based on presence of elevated ECV and of any LGE. Subsequent HF admission and any death were ascertained. Their relationship with ECV was examined separately and as a composite with Cox proportional hazard models. Results: Of 1,604 serial patients with T1 maps, 1,047 were eligible after exclusions and followed over a median 10.5 (interquartile range 5.4, 21.4) months. Patients with elevated ECV had an increased risk for death (hazard ratio [HR] 2.60, 95% confidence interval [CI] 1.78 to 3.79)), HF admissions (HR 1.97, 95% CI 1.48 to 2.61), and combined endpoint (HR 2.14, 95% CI 1.69 to 2.70) regardless of LGE presence (Table). After adjustments for covariates, the relationship persisted for death (HR 1.86, 95% CI 1.24 to 2.79), hospitalization (HR 1.54, 95% CI 1.13 to 2.10), and combined endpoints (HR 1.60, 95% CI 1.24 to 2.07). Conclusion: Extracellular volume fraction measures were associated with heart failure outcomes, despite censoring of replacement fibrosis segments and even among patients without any replacement fibrosis. ECV may have a synergistic role with replacement fibrosis in heart failure risk assessment.
Abstract MP076: Angiographic Coronary Artery Disease Severity and Risk of Mental and Conventional Stress Induced Myocardial Ischemia
Authors: Muhammad Hammadah, Naser Abdelhadi, Shuyang Fang, Zakaria Almuwaqqat, Ayman Alkhoder, Mazen Ghafeer, Hawkins C Gay, Ijeoma Ibeanu, Wesley T O’Neal, Samah Sullivan, Ayman Samman Tahhan, Heval Mohamed Kelli, Levantsevych Oleksiy, Malik Obideen, Pratik Pimple, Pratik Sandesara, ibhar almheid, Kobina Wilmot, Ronnie Ramadan, Amit J Shah, J. Douglas Bremner, Paolo Raggi, David Sheps, Arshed Quyyumi, Viola Vaccarino
Journal: Circulation (2017)

Background: Mental stress induced myocardial ischemia (MSIMI) is linked to increased risk of adverse cardiovascular outcomes, but its mechanisms are thought to be different from those of conventional stress-induced ischemia (CSIMI). Specifically, whether MSIMI is associated with more severe underlying obstructive coronary artery disease (CAD) is unclear. We investigated the association between angiographically-defined CAD severity and both MSIMI and CSIMI with a hypothesis that, CAD severity will be linked to CSIMI, but not MSIMI. Methods: A total of 273 patients with stable CAD, aged 51±7 years, 49% female, who survived a myocardial infarction (MI) within the past 8 months (median 167±52 days) were enrolled in the Myocardial Infarction and Mental Stress 2 (MIMS-2) study. The coronary angiogram performed during the index MI hospitalization was used to assess CAD severity. Coronary artery obstruction was assessed by counting the number of diseased vessels with 70% stenosis (DV70%) and using the Gensini Score (GS) after correcting for revascularized vessels. Patients underwent 99mTc sestamibi myocardial perfusion imaging during mental stress, using a public speaking task, and during conventional stress test, using exercise or pharmacological stress. MSIMI and CSIMI were defined as a new or worsening impairment in myocardial perfusion using a 17-segment model. Results: A total of 68 (26%) patients developed CSIMI, while 46 (17%) developed MSIMI. Median DV70% and GS were 0 (0-1), and 3 (0-12), respectively. Using logistic regression models, and after adjustment for age, gender, hypertension, hyperlipidemia and diabetes, obstructive CAD was associated with increased risk of CSIMI [OR(95%CI) of 1.54 (1.02 - 2.31) for DV70% and 1.25 (1.03-1.53), for GS], but not MSIMI [OR(95%CI) of 0.93 (0.56 - 1.53) for DV70%, and 0.94 (0.75-1.18) for GS]. Conclusion: Although CSIMI is linked to underlying coronary obstruction, MSIMI is independent of CAD severity among post- MI patients. Other mechanisms are likely responsible for MSIMI post MI.
Hydrochlorothiazide and the Risk of Malignant Melanoma
Authors: Bert-Jan H. van den Born, Rik Olde-Engberink, Liffert Vogt
Journal: JAMA Internal Medicine (2018)

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 Internal Medicine 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 Internal Medicine journal
Abstract 18399: Higher Plasma Cxcl12 Levels Are Causally Associated With Increased Risk of Coronary Heart Disease
Authors: Wei Zhao, Jing Hua Zhao, Asif Rasheed, Muredach Reilly, Robert Luben, Anders Malarstig, Kay-Tee Khaw, John Danesh, Nick Wareham, Daniel Rader, Danish Saleheen
Journal: Circulation (2016)

Introduction: Although CXCL12 (10q11) is one of the early coronary heart disease (CHD) loci discovered in genome-wide association studies, the directional impact of the CXCL12 pathway on CHD remain...
Targeting nuclear receptor NR4A1–dependent adipocyte progenitor quiescence promotes metabolic adaptation to obesity
Authors: Yang Zhang, Alexander J. Federation, Soomin Kim, John P. O’Keefe, Mingyue Lun, Dongxi Xiang, Jonathan D. Brown, Matthew L. Steinhauser
Journal: Journal of Clinical Investigation (2018)

Adipocyte turnover in adulthood is low, suggesting that the cellular source of new adipocytes, the adipocyte progenitor (AP), resides in a state of relative quiescence. Yet the core transcriptional regulatory circuitry (CRC) responsible for establishing a quiescent state and the physiological significance of AP quiescence are incompletely understood. Here, we integrate transcriptomic data with maps of accessible chromatin in primary APs, implicating the orphan nuclear receptor NR4A1 in AP cell-state regulation. NR4A1 gain and loss of function in APs ex vivo decreased and enhanced adipogenesis, respectively. Adipose tissue of Nr4a1–/– mice demonstrated higher proliferative and adipogenic capacity compared with that of WT mice. Transplantation of Nr4a1–/– APs into the subcutaneous adipose tissue of WT obese recipients improved metrics of glucose homeostasis relative to administration of WT APs. Collectively, these data identify NR4A1 as a previously unrecognized constitutive regulator of AP quiescence and suggest that augmentation of adipose tissue plasticity may attenuate negative metabolic sequelae of obesity.
Abstract 14205: Left Ventricular Untorsion Rate Evaluated by a Three-dimensional Speckle Tracking Echocardiography is a Novel Echo Index of Relaxation in Patients With Hypertension and Preserved Ejection Fraction
Authors: Masanori Kawasaki, Ryuhei Tanaka, Takashi Yoshizane, Shingo Minatoguchi, Hirotaka Miwa, Koji Ono, Maki Nagaya, Shuntaro Horio, Toshiyuki Noda, Hiroshige Ohashi, Sachiro Watanabe, Shinya Minatoguchi
Journal: Circulation (2016)

Introduction: Early relaxation of left ventricle (LV) is characterized by rapid torsional recoil of LV. Predominant epicardial stretch along myofibers during isovolumic relaxation (IVR) appears to ...
The Patient Experience and Use of Telemetry Monitoring—Reply
Authors: Garth W. Strohbehn, Raymond Y. Yeow, Amit K. Pahwa
Journal: JAMA Internal Medicine (2018)

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 Internal Medicine 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 Internal Medicine journal
Letter to the Editor: Proton Pump Inhibitor Use and Risk of Hepatocellular Carcinoma
Authors: Shih‐Wei Lai
Journal: Hepatology (2018)

Potential conflict of interest: Nothing to report. To the Editor: One cohort study using the Taiwan National Health Insurance Research Database conducted by Kao et al. published in hepatology reported that proton pump inhibitor use was not associated with the risk of developing hepatocellular carcinoma in patients with chronic hepatitis B infection or chronic hepatitis C infection.1 The findings were compatible with our cohort analysis using the Taiwan National Health Insurance Research Database showing no association between proton pump inhibitor use and hepatocellular carcinoma.2 In contrast, a recent case‐control study using the Taiwan National Health Insurance Research Database conducted by Shao et al. reported that proton pump inhibitor use might increase the risk of hepatocellular carcinoma in patients without hepatitis B infection or hepatitis C infection (odds ratio, 2.86; 95% confidence interval, 2.69‐3.04).3 Because of conflicting results in these observational studies, some points should be discussed. First, at least 90% of patients with hepatocellular carcinoma in Taiwan are associated with chronic hepatitis B infection or chronic hepatitis C infection.4 Therefore, any study investigating the medication's effect on the risk of hepatocellular carcinoma in Taiwan should make an adjustment for these two viral infections. The study by Kao et al. has such strength, but that by Shao et al. doesn’t. Second, all proton pump inhibitors act on the parietal cells of the stomach, but no study available shows that proton pump inhibitors can act on liver cells. There is also not a rational hypothesis about the link between proton pump inhibitors and hepatocellular carcinoma. It is difficult to convince the readers regarding proton pump inhibitor use on the risk of hepatocellular carcinoma. Last, Shao et al. explained that the database they used was different from the database we used.5 To the best of our knowledge, insurance reimbursement claims data in Taiwan were available for public access. It is less likely that researchers can access a different database in Taiwan. The only difference is the years of the database studied. Based on our study and that of Kao et al., proton pump inhibitor use is not associated with the risk of developing hepatocellular carcinoma. Currently, it is not necessary to stop using proton pump inhibitors because of concerns about the risk of hepatocellular carcinoma.
Different Originating Cells Underlie Intertumoral Heterogeneity in Lung Neuroendocrine Tumors
Authors: Karine Pozo, Demetra P. Kelenis, John D. Minna, Jane E. Johnson
Journal: Cancer Discovery (2018)

Abstract Summary: Studies in genetically engineered mouse models of neuroendocrine lung cancer suggest that differences in cells of origin underlie subtype variations in this class of cancers. These findings highlight the concept that the same driver mutations introduced into different cells of origin lead to tumors with the same histology but dramatically different metastatic programs and potentially different therapeutic responses. Cancer Discov; 8(10); 1216–8. ©2018 AACR. See related article by Yang et al., p. 1316.
The importance of response to chemotherapy in advanced squamous non-small cell lung cancer (NSCLC).
Authors: Vera Hirsh, Yin Wan, Scott Whiting, Teng Jin Ong, Marc Botteman
Journal: Journal of Clinical Oncology (2015)

e17694 Background: A phase III clinical trial demonstrated that nab-paclitaxel plus carboplatin significantly improved objective overall response rate compared with solvent-based paclitaxel plus carboplatin in patients (pts) with NSCLC. This post hoc analysis of the squamous patient subgroup examined the survival and quality-of-life implications of achieving response in this population. Methods: Pts with an objective confirmed partial or complete response (RS) at or prior to the first tumor response assessment at six weeks (ie, landmark) were compared to those without a response (non-RS) in postlandmark progression-free survival (PFS), overall survival (OS), Q-TWiST, and Functional Assessment of Cancer Therapy–Taxane (FACT-T) score by cycle. Results: Of the 422 pts with squamous NSCLC, RS pts (n = 76) were not significantly different from non-RS pts (n = 346) except that a higher percentage of them had stage IIIB disease (P< 0.001). Stage-adjusted and unadjusted survival and Q-TWiST outcomes were significantly better in RS than non-RS pts. In the adjusted results, RS pts experienced significantly better postlandmark median OS (+4.6 mo [13.2 vs 8.6 mo]; HR = 0.646; P= 0.005), mean OS (+3.1 mo [13.5 vs 10.4 mo; 95% CI, 1.5-4.7]), median PFS (+1.4 mo [5.5 vs 4.1 mo]; HR = 0.613; P= 0.005), mean PFS (+1.9 mo [7.4 vs. 5.5 mo; 95% CI, 0.6-3.4]), and Q-TWiST (+2.5 mo [95% CI, 1.2-3.8]). RS pts had less deterioration in total FACT-T at every time point, with results significantly better at the 8th (P= 0.037), 9th (P= 0.018), and 10th (P= 0.006) treatment cycles. Conclusions: nab-paclitaxel plus carboplatin significantly improved response in pts with squamous NSCLC. This analysis showed thatresponse to doublet chemotherapy in squamous NSCLC was associated with significantly better quality of life, survival, and quality-adjusted survival, implying that response is an important endpoint for assessing outcomes in this population. Clinical trial information: NCT00540514.
Nicotine causes methylation of FHIT gene in normal esophageal epithelial cell lines
Authors: Toshiya Soma, Yutaka Shimada, Junichi Kaganoi, Atsushi Itami, Masayuki Imamura
Journal: Cancer Research (2004)

4177   Backgrounds and Aims: Transcriptional silencing of tumor suppressor genes in association with DNA methylation contributes to malignant transformation. Methylation of fragile histidine triad the(FHIT) gene, chromosome region 3p14.2, was frequently reported in several cancers. It suggested that methylation of the FHIT gene may play an important role in the early stage of esophageal squamous cell carcinogenesis. We previously reported that methylation of the 5Af CpG island of FHIT gene correlated with transcriptional inactivation of esophageal squamous cell carcinoma (ESCC). On the other hand, methylation of FHIT gene was found in lung cancer patients who smoke heavily. However, the processes that initiate methylation are unknown. In this study, we confirmed that nicotine induced methylation of FHIT gene is normal in the esophageal epithelial cell (NEEC). Materials and Methods: ESCC cells (KYSEs) and NEEC cells (KNECs and HEECs), established in our laboratory under informed consent, were used to investigate. Unmethylated DNAs were obtained from KYSE-410 and KYSE-590 and methylated DNAs were obtained from KYSE-150 (H.Tanaka et al., Cancer Research. 1998). NEEC cells were incubated with or without nicotinic stimulation (100mM). 100mM was the nicotinic concentration of saliva of a smoker (25 cigarettes per day) (C.Feyerabend et al., British Journal of Clinical Pharmacology 1985). After bisulphate treatment of genomic DNA, methylation of promoter region of FHIT was analyzed by methylation-specific PCR (MSP) and by sequence. Results: Our findings show that, without nicotinic stimulation, methylation of FHIT gene was not found in NEEC cells. Secondly, with nicotinic stimulation, methylation of FHIT gene was found in NEEC cells within 24 hrs after stimulation. Finally, this methylation of FHIT gene was not found after removing the nicotinic stimulation. Conclusion: In conclusion, the FHIT gene was found to be one of the tumor suppressor genes. Our data suggests that nicotine caused carcinogenesis in the early stage by methylation of the FHIT gene in the esophageal mucosa. Furthermore, methylation caused by nicotine of the FHIT gene was reversible. However, further investigation is needed in order to evaluate mechanism of carcinogenes is in esophageal mucosa.
A phase I and pharmacokinetic study of paclitaxel and carboplatin combined with sodium selenite in patients with gynecologic malignacies
Authors: Murugesan K. Gounder, Darlene Gibbon, Chidam A. Kumar, Novlette Simmons, Brian Buckley, Ruimin Xie, Yong Lin, Weichung Shih, Gerald D. Frenkel, Paula Caffrey, Eric H. Rubin, Lorna Rodrigeuz-Rodriguez
Journal: Cancer Research (2005)

3983  Drug resistance to platinum-based regimens remains a major factor that limits clinical effectiveness in several cancers, including gynecologic malignancies. In animal and ovarian xenografts models selenium was reported to protect against nephrotoxicity and development of resistance to cisplatin (Camargo et al 2001, Caffrey et al 2000). Therefore, we developed a phase I clinical trial investigating the combination of sodium selenite (SS) with carboplatin. The objective of this phase I study is to determine the dose-limiting toxicity and maximum-tolerated dose of SS when given with carboplatin/paclitaxel to chemo-naive patients with advanced gynecologic malignancies. Since selenium is known to alter glomerular filtration rate (GFR), and GFR is widely used to determine the dose of carboplatin, the study was also designed to determine whether selenium alters carboplatin pharmacokinetic (PK) parameters. On day 1 selenium was administered intravenously (i.v.) for 5 hours, and on day 3, paclitaxel 175 mg/m2 was infused i.v. over 3 hours, followed by i.v. carboplatin AUC 5 (Calvert method) for 30 min. During the first cycle carboplatin dose was AUC 5, and during subsequent cycles carboplatin AUC was escalated to 6. SS was escalated in cohorts of 3 patients. Plasma and plasma ultrafiltrate were analyzed for carboplatin concentration (using inductively coupled plasma-mass spectrometer, ICP-MS at 195.8 m/z on a Thermal-Element X5 instrument). Eleven patients have been enrolled at SS doses of 50 μg (n=3), 100 μg (n=6), and 200 μg (n=2) and treated for a total of 53 cycles. Grade 3/4 toxicities included neutropenia (4/53 cycles), thrombosis/embolism (1/53), and nausea/vomiting (1/53). One complete response, 3 partial responses, and 1 stable disease, were observed in 5 patients with measurable disease. The average observed AUCs on cycle 1 were 4.4 (range 3.8-5.7) and on cycle 2 were 5.5 (3.3 - 7.5). These results indicate that at current doses, SS can be coadministered safely with carboplatin. Further, at these doses there is no significant alteration of predicted carboplatin AUC by SS. Supported by grant from New Jersey Commission on Cancer Research
Gene fitness landscape of group A streptococcus during necrotizing myositis
Authors: Luchang Zhu, Randall J. Olsen, Stephen B. Beres, Jesus M. Eraso, Matthew Ojeda Saavedra, Samantha L. Kubiak, Concepcion C. Cantu, Leslie Jenkins, Amelia R. L. Charbonneau, Andrew S. Waller, James M. Musser
Journal: Journal of Clinical Investigation (2019)

Necrotizing fasciitis and myositis are devastating infections characterized by high mortality. Group A streptococcus (GAS) is a common cause of these infections, but the molecular pathogenesis is poorly understood. We report a genome-wide analysis using serotype M1 and M28 strains that identified GAS genes contributing to necrotizing myositis in nonhuman primates (NHP), a clinically relevant model. Using transposon-directed insertion-site sequencing (TraDIS), we identified 126 and 116 GAS genes required for infection by serotype M1 and M28 organisms, respectively. For both M1 and M28 strains, more than 25% of the GAS genes required for necrotizing myositis encode known or putative transporters. Thirteen GAS transporters contributed to both M1 and M28 strain fitness in NHP myositis, including putative importers for amino acids, carbohydrates, and vitamins and exporters for toxins, quorum-sensing peptides, and uncharacterized molecules. Targeted deletion of genes encoding 5 transporters confirmed that each isogenic mutant strain was significantly (P < 0.05) impaired in causing necrotizing myositis in NHPs. Quantitative reverse-transcriptase PCR (qRT-PCR) analysis showed that these 5 genes are expressed in infected NHP and human skeletal muscle. Certain substrate-binding lipoproteins of these transporters, such as Spy0271 and Spy1728, were previously documented to be surface exposed, suggesting that our findings have translational research implications.
DAY-CASE BRAIN TUMOUR BIOPSY: OUR EXPERIENCE OVER EIGHT YEARS
Authors: Fozia Saeed, Sandeep Solanki, Gnanamurthy Sivakumar, Rob Corns, John Goodden, Paul Chumas, Simon Thomson
Journal: Neuro-Oncology (2018)

Day-case brain tumour biopsy is an established practice in only a limited number of UK neurosurgical centres. The reluctance to adopt this protocol may be due to the lack of published evidence on its safety. We present our experience following 8 years practice. All patients undergoing brain tumour biopsy between November 2009–2017 were included. Subjects were identified through hospital operations database and their electronic case notes. 447 biopsies were performed over 8 years with 160 intended as day-case and 135 actual day-case procedures, revealing a failure rate of 15.6% (25). Mean age was 58 years. Pathology included low grade tumours (26), high grade tumours (95), lymphoma (21), metastases (6) and non-tumours (12). Locations were broadly categorised as frontal (69), parietal (40), temporal (35), occipital (3) or posterior fossa (13). Causes for failed day-cases included post-operative haematoma, delayed imaging and new neurological deficit. Mortality rate was 0%. Re-admission rate was 3% due to seizures (3) and wound infection (1). Close surveillance post-operatively permits for prompt delivery of care together with an enhanced patient experience. As demonstrated and consistent with other centres’ experience, this is a safe and effective technique. Day-case surgery helps meet the modern demands of the NHS by improving patient flow and relieving bed pressures provided a bespoke day-case pathway exists.