tbuckley/cabot-search huggingface dataset:
Abstract 16793: Association of Impairment of Myocardial Metabolism and Ventricular Arrhythmic Events in Patients With Hypertrophic Cardiomyopathy by Single Photon Emission Computed Tomography With A Solid-state Dedicated Cardiac Camera
Authors: Yuko Utanohara, Nobuo Iguchi, Harutoshi Tamura, Morimasa Takayama, Jun Umemura, Tetsuya Sumiyoshi, Hitonobu Tomoike
Journal: Circulation (2015)

Background: Ventricular arrhythmic events have adverse implications for patients with hypertrophic cardiomyopathy (HCM). However, little has been reported on the relationship between myocardial metabolic abnormalities and ventricular arrhythmia. Iodine-123-beta-methyl iodophenyl-pentadecanoic acid (BMIPP) is used to assess myocardial metabolic abnormalities. A solid-state dedicated cardiac camera (D-SPECT) provides precise assessment of abnormal uptake and reduction of radiation dose in HCM by high sensitivity and high spatial resolution. Objective: The aim of this study was to evaluate the utility of BMIPP using D-SPECT for prediction of ventricular arrhythmic events in patients with HCM. Methods: We studied 125 consecutive HCM patients who underwent dual SPECT with D-SPECT using BMIPP and technetium-99m sestamibi (MIBI) or thallium-201 (TL). Reduced uptake on the BMIPP image compared with the MIBI / TL perfusion image was defined as perfusion-metabolic mismatch. In quantitative analysis, a polar map was divided into 17 segments and the score of each segment was derived from the average percent uptake. Mismatch scores (MS) were calculated from the differences between the BMIPP and MIBI / TL scores. Ventricular arrhythmic events were defined as ventricular tachycardia, appropriate ICD therapy and sudden cardiac death. Results: Patients with the obstructive type of HCM had a significantly higher MS than those with the non-obstructive type. Significant correlation between the MS and left ventricular mass (r = 0.28, p &lt; 0.01) and maximal wall thickness (r = 0.27, p &lt; 0.01) were observed. MS was significantly higher in patients with ventricular arrhythmic events than in those without events (p &lt; 0.05). In ROC analysis, patients with a higher MS had significantly more arrhythmic events than those with a lower MS (cutoff value: 74.5, AUC: 0.644, p &lt; 0.01). In multivariate analysis, the MS was identified as an independent factor associated with ventricular arrhythmic events (p &lt; 0.01). Conclusions: Abnormal uptake of BMIPP in patients with HCM is associated with ventricular arrhythmic events. Dual SPECT with D-SPECT using BMIPP and MIBI / TL is a useful modality for risk stratification and may reveal the existence of substrate for ventricular arrhythmia.
Biomarker-integrated study of single agent targeting molecular alterations of PI3KCA, MET, ALK, ROS1, KRAS, NRAS or BRAF in advanced NSCLC: Phase 2 umbrella trial in China (CTONG1505)
Authors: Q. Zhou, X.-C. Zhang, H.-Y. Tu, B. Gan, B.-C. Wang, C.-R. Xu, H.-J. Chen, M.-Y. Zheng, Z. Wang, X.-Y. Bai, Y.-L. Sun, A. Myers, X. Lv, Y. Chakrabcorti, S. Zhao, J.-J. Yang, Y.-L. Wu
Journal: Annals of Oncology (2018)
Breakthrough Therapy Designation for New Drugs—Reply
Authors: Jeremy Puthumana, Joshua D. Wallach, Joseph S. Ross
Journal: JAMA (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 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
3-Methyl-4-nitrophenol triggers nasal allergy by modulating dendritic cell properties
Authors: Xiao-Yu Liu, Yong-Jin Wu, Li-Juan Song, Xian-Hai Zeng, Shuai Wang, Jiang-Qi Liu, Li-Hua Mo, Xiao-Rui Geng, Li-Teng Yang, Rui-Di Xie, Xiao-Wen Zhang, Zhi-Gang Liu, Ping-Chang Yang
Journal: Journal of Allergy and Clinical Immunology (2018)
Sunitinib-suppressed miR-452-5p facilitates renal cancer cell invasion and metastasis through modulating SMAD4/SMAD7 signals
Authors: Wei Zhai, Saiyang Li, Jin Zhang, Yonghui Chen, Junjie Ma, Wen Kong, Dongkui Gong, Junhua Zheng, Wei Xue, Yunfei Xu
Journal: Molecular Cancer (2018)

Abstract Purpose Although microRNAs (miRNAs) were revealed as crucial modulators in tumor metastasis and target therapy, our understanding of their roles in metastatic renal cell carcinoma (mRCC) and Sunitinib treatment was limited. Here we sought to identify human miRNAs that acted as key regulators in renal cancer metastasis and Sunitinib treatment. Experimental design We focused on 2 published microarray data to select out our anchored miRNA and then explored the roles of miR-452-5p both in vitro and in vivo, which was downregulated after Sunitinib treatment while upregulated in metastasis renal cell carcinoma (RCC) tissues. Results Here, we discovered that treating with Sunitinib, the targeted receptor tyrosine kinase inhibitor (TKI), inhibited renal cancer cell migration and invasion via attenuating the expression of miR-452-5p. The novel identified miR-452-5p was upregulated and associated with poor prognosis in RCC. Preclinical studies using multiple RCC cells and xenografts model illustrated that miR-452-5p could promote RCC cell migration and invasion in vitro and in vivo. Mechanistically, P65 could directly bind to the miR-452-5p promoter and thus transcriptionally induce miR-452-5p expression, which led to post-transcriptionally abrogate SMAD4 expression, thus inhibition of its downstream gene SMAD7. Conclusion Our study presented a road map for targeting this newly identified miR-452-5p and its SMAD4/SMAD7 signals pathway, which imparted a new potential therapeutic strategy for mRCC treatment.
The Pediatric Guideline Adherence and Outcomes (PEGASUS) programme in severe traumatic brain injury: a single-centre hybrid implementation and effectiveness study
Authors: Monica S Vavilala, Mary A King, Jen-Ting Yang, Scott L Erickson, Brianna Mills, Rosemary M Grant, Carolyn Blayney, Qian Qiu, Randall M Chesnut, Kenneth M Jaffe, Bryan J Weiner, Brian D Johnston
Journal: The Lancet Child & Adolescent Health (2018)
Monitoring of disseminated pleural tumors using non-invasive bioluminescent in vivo imaging system
Authors: Seiji Matsumoto, Fumihiro Tanaka, Hiromichi Katakura, Masashi Adachi, Shinya Kimura, Taira Maekawa, Hiromi Wada
Journal: Cancer Research (2005)

Proc Amer Assoc Cancer Res, Volume 46, 2005

1052 

Background: Malignant pleural effusion caused by disseminated pleural tumors is a common and critical issue in patients with advanced malignancies. Pleurodesis is usually performed for the control, but it sometimes fails to control or cause some complications. Docetaxel (Taxotere) is the second member of the taxane class of cytotoxic agents to reach clinical use. Preclinical cytotoxic activity was evident in mice bearing ovarian carcinoma xenografts implanted intraperitoneally and treated with intraperitoneal docetaxel. This present study was conducted to examine the efficacy of intrapleural docetaxcel administration in disseminated pleural-tumor models. Disseminated pleural-tumor models commonly use parameters such as tumor weight or volume to assess disease burden. These measurements needs animal to be sacrifice and do not allow for serial observation of tumor growth in the same animal. For theses reason, we have opted to investigate luciferase as a bioluminescent marker for disseminated disease. Methods: A stable non-small cell carcinoma cell line transfected with the firefly Luciferase gene (A549 - Luc) was used. BALBc Nu/Nu mice were injected with 5,000,000 cotransfected A549 into the pleural space. When disseminated pleural tumors were established, we started repeated intrapleural administration of docetaxcel (12.5mg/kg/day, once a week for 6 weeks); the optimal schedule and dose, which caused no significant body weight-loss, was determined in preliminary experiments. All bioluminescent data were collected and analyzed with a Xenogen IVIS® system. Results: Disseminated pleural-tumor could be imaged by IVIS® system in real time. A statistical difference in mean tumor bioluminescence between the treated and untreated groups was found at day 17 after treatment started. Repeated intrapleural administration of docetaxcel significantly prolonged survivals (p=0.002). Conclusions: IVIS® system was useful in monitoring disseminated pleural-tumor and repeated intrapleural administration of docetaxcel was effective in in vivo disseminated pleural tumor models.
Healthy volunteers' perceptions of risk in US Phase I clinical trials: A mixed-methods study
Authors: Jill A. Fisher, Lisa McManus, Marci D. Cottingham, Julianne M. Kalbaugh, Megan M. Wood, Torin Monahan, Rebecca L. Walker
Journal: PLoS Medicine (2018)

Background There is limited research on healthy volunteers' perceptions of the risks of Phase I clinical trials. In order to contribute empirically to long-standing ethical concerns about healthy volunteers' involvement in drug development, it is crucial to assess how these participants understand trial risks. The objectives of this study were to investigate (1) participants' views of the overall risks of Phase I trials, (2) their views of the risk of personally being harmed in a trial, and (3) how risk perceptions vary across participants' clinical trial history and sociodemographic characteristics. Methods and findings We qualitatively and quantitatively analyzed semi-structured interviews conducted with 178 healthy volunteers who had participated in a diverse range of Phase I trials in the United States. Participants had collective experience in a reported 1,948 Phase I trials (mean = 10.9; median = 5), and they were interviewed as part of a longitudinal study of healthy volunteers' risk perceptions, their trial enrollment decisions, and their routine health behaviors. Participants' qualitative responses were coded, analyzed, and subsequently quantified in order to assess correlations between their risk perceptions and demographics, such as their race/ethnicity, gender, age, educational attainment, employment status, and household income. We found that healthy volunteers often viewed the overall risks of Phase I trials differently than their own personal risk of harm. The majority of our participants thought that Phase I trials were medium, high, or extremely high risk (118 of 178), but most nonetheless felt that they were personally safe from harm (97 of 178). We also found that healthy volunteers in their first year of clinical trial participation, racial and ethnic minority participants, and Hispanic participants tended to view the overall trial risks as high (respectively, Jonckheere-Terpstra, −2.433, p = 0.015; Fisher exact test, p = 0.016; Fisher exact test, p = 0.008), but these groups did not differ in regard to their perceptions of personal risk of harm (respectively, chi-squared, 3.578, p = 0.059; chi-squared, 0.845, p = 0.358; chi-squared, 1.667, p = 0.197). The main limitation of our study comes from quantitatively aggregating data from in-depth interviews, which required the research team to interpret participants' nonstandardized risk narratives. Conclusions Our study demonstrates that healthy volunteers are generally aware of and reflective about Phase I trial risks. The discrepancy in healthy volunteers' views of overall and personal risk sheds light on why healthy volunteers might continue to enroll in clinical trials, even when they view trials on the whole as risky.
Intake of selected food groups and beverages and adult acute myeloid leukemia
Authors: Yulin Li, Kirsten B. Moysich, Maria R. Baer, Joli Weiss, John R. Brasure, Saxon Graham, Susan E. McCann
Journal: Cancer Research (2006)

2005  Acute myeloid leukemia (AML) is the more common acute leukemia in adults. Except for environmental and occupational risk factors such as ionizing radiation and benzene exposure, the etiology of the disease remains poorly understood. Evidence for the role of diet in AML etiology is inconsistent and few epidemiological studies have explored the association between diet and AML in adults. To address this gap, we conducted a hospital-based case-control study at Roswell Park Cancer Institute and examined intake of selected food groups and beverages and AML risk among 111 cases (56 men, 55 women) and 439 control patients with non-neoplastic diseases (221 men, 218 women). Extensive epidemiologic data were collected using a self-administered questionnaire; diet was queried with a 44-item food frequency questionnaire. Odds ratios (OR) and 95% confidence intervals (CI) were computed with unconditional logistic regression stratified by gender, adjusting for age, education, energy intake, and smoking status. Among women, we found a significantly reduced risk associated with higher intake of milk (OR= 0.25, 95%CI= 0.08-0.73). Regular tea intake was associated with risk reductions in women (OR= 0.50, 95%CI=0.23-1.09) and men (OR= 0.34, 95%CI=0.14-0.82). Compared to the lowest categories of intakes, statistically significant increased risks were observed among women with the highest intakes of beer (OR=2.48, 95%CI = 1.05-5.85), wine (OR=2.32, 95% CI=1.05-5.09), and beef (OR 4.78, 95% CI 1.35-16.94). Borderline increased risks were associated with the highest intakes of coffee in women (OR= 2.08, 95%CI=0.98-4.39), but not among men. Although we were limited by a small sample size, our findings suggest that higher intakes of regular tea and milk may be important in reducing risk of AML, and higher intakes of beef, coffee, beer and wine may increase risk of AML in adult women. Further research is warranted to identify gender-specific characteristics (e.g., reproductive factors) that might explain our observed differences in effects between men and women.
NHS staff shortages could reach 250 000 by 2030 without urgent action, experts warn
Authors: Gareth Iacobucci
Journal: BMJ (2018)

The NHS could be short of a quarter of a million healthcare staff by 2030 unless urgent and sustained action is taken to improve recruitment and retention, a group of leading experts have warned.

In a briefing paper1 the King’s Fund, the Health Foundation, and the Nuffield Trust predicts that NHS staff shortages in England could increase from 100 000 at present to almost 250 000 by 2030 if not dealt with. This could reach 350 000 if the NHS continues to lose staff and cannot attract skilled workers from abroad, the analysis …
Evaluation of the Short‐, Mid‐, and Long‐Term Effects of Tofacitinib on Lymphocytes in Patients With Rheumatoid Arthritis
Authors: Ronald van Vollenhoven, Eun Bong Lee, Sander Strengholt, Christopher Mojcik, Hernan Valdez, Sriram Krishnaswami, Pinaki Biswas, Irina Lazariciu, Anasuya Hazra, James D. Clark, Jennifer Hodge, Lisy Wang, Ernest Choy
Journal: Arthritis & Rheumatology (2018)

Objective Tofacitinib is an oral JAK inhibitor for the treatment of rheumatoid arthritis (RA). Altered lymphocyte cell counts and a potential association with increased infection rates have been reported in RA patients treated with JAK inhibitors. This analysis was undertaken to evaluate the short‐, mid‐, and long‐term effects of tofacitinib on lymphocytes and infection rates in patients with RA. Methods In this post hoc analysis, absolute lymphocyte counts (ALCs) were obtained from phase III studies (12–24 months; n = 717–958) and phase I/II/III/long‐term extension studies of tofacitinib (≤117 months) (All RA population; n = 7,061); lymphocyte subset counts (LSCs) were from phase II studies (1.5–6 months’ exposure; n = 236–486), an ORAL Sequel vaccine substudy (~22 months; n = 198), and an ORAL Sequel lymphocyte substudy (~50 months; n = 55–1,035) of tofacitinib. The reversibility of ALC/LSC changes was evaluated. The relationship of ALC and LSC to infections was analyzed in the All RA population. The value of monitoring ALC alone was assessed by examining correlations between ALCs and LSCs. Results Tofacitinib treatment resulted in an initial increase in ALC versus pretreatment baseline, which gradually declined to steady state by ~48 months. CD4+ and CD8+ T cell counts decreased over long‐term treatment, and ALC and LSC changes were reversible upon treatment cessation. Patients with ALCs of &lt;500 cells/mm 3 had an increased risk of serious infections. There was no strong association between CD4+ T cell, CD8+ T cell, B cell, or natural killer cell counts and serious infection incidence rates. ALC and CD4+ or CD8+ T cell counts correlated well (R = 0.65–0.86). Conclusion Our findings indicate that monitoring of ALC alone appears to be adequate to assess infection risk in tofacitinib‐treated patients with RA.
Body fat distribution, diabetes, and prostate cancer in afro-caribbean men: the tobago prostate cancer survey
Authors: Clareann Bunker, Kathleen McHugh-Pemu, Michael Okobia, Joseph Zmuda, Victor Wheeler, Alan Patrick, Jane Cauley
Journal: Cancer Research (2007)

2502  A positive association between body fat and prostate cancer has been observed, though studies are inconsistent. Paradoxically, diabetes appears to be protective against prostate cancer. We examined the association of body fat distribution and diabetes with prostate cancer among Afro-Caribbean men on the Island of Tobago.  Participants comprised 226 men, aged 50-79 years, with screening-detected prostate cancer and 666 men with normal screening results (normal digital rectal examination (DRE) and serum prostate specific antigen (PSA)  ≤ 4 ng/ml) ascertained in a population-based screening study. Standard protocols were used to collect anthropometric measures and self-reported history of diabetes. Regional body composition was measured by dual x-ray absorptiometry (DXA). Unconditional logistic regression was used to identify potential independent predictors of prostate cancer risk.  After controlling for age, prostate cancer cases and controls were similar in anthropometric measurements and in DXA estimates of lean and fat mass in the arm, leg, and trunk, except for percent trunk fat which was marginally higher in cases than controls (50.5 vs. 50.1, respectively, p = 0.085). History of diabetes was reported by 157 men. History of diabetes was marginally protective against prostate cancer (OR = 0.66, p = 0.065). However, there was a strong interaction between diabetes and percent trunk fat (p=0.008) for prostate cancer. Compared with men without diabetes and percent trunk fat below the median, age-adjusted risk was much lower for men with diabetes and percent trunk fat below the median (OR=0.24, 95%CI 0.10-0.58), while risk among men with percent trunk fat above the median was similarly elevated in men with diabetes (OR=1.32, 95%CI 0.92-1.90) and without diabetes (OR=1.30, 95%CI 0.76-2.22). No interactions were observed in similar analyses of body weight, body mass index, waist circumference or DXA estimated total body percent fat.  These results support an association between prostate cancer and central body fat deposition and diabetes which is modified by diabetes only in men with lower trunk fat. This interaction may explain some of the inconsistencies among previous studies. Further studies are needed to understand hormonal and other factors which may underlie this complex association.
Implications of Medicare Coverage for Magnetic Resonance Imaging in Patients With Capped or Epicardial Leads
Authors: Daniel B. Kramer, Bernard Lo, Robert J. Russo
Journal: JAMA Cardiology (2018)

This Viewpoint describes reasons why the Centers for Medicare and Medicaid Services should revisit a coverage decision affecting the ability of patients with pacemakers or implantable cardioverter-defibrillators to access magnetic resonance imaging.
Reduced-Intensity Allogeneic HSCT for Children and Adolescents/Young Adults with CML: A Study from the Adult and Pediatric CML Working Group of the Japan Society for Hematopoietic Cell Transplantation
Authors: Hiroyuki Shimada, Akihiko Tanizawa, Takeshi Kondo, Hideki Muramatsu, Masahiro Yasui, Arinobu Tojo, Tokiko Nagamura-Inoue, Tetsuya Eto, Aiko Igarashi, Heiwa Kanamori, Maho Sato, Maiko Noguchi, Tatsuo Ichinohe, Masami Inoue, Koji Kato, Yoshiko Atsuta, Kazuteru Ohashi
Journal: Blood (2018)
Placebo vs Amoxicillin for Nonsevere Fast-Breathing Pneumonia in Malawian Children Aged 2 to 59 Months
Authors: Amy Sarah Ginsburg, Tisungane Mvalo, Evangelyn Nkwopara, Eric D. McCollum, Chifundo B. Ndamala, Robert Schmicker, Ajib Phiri, Norman Lufesi, Rasa Izadnegahdar, Susanne May
Journal: JAMA Pediatrics (2018)

<h3>Importance</h3> Pneumonia is the leading infectious killer of children. Rigorous evidence supporting antibiotic treatment of children with nonsevere fast-breathing pneumonia in low-resource African settings is lacking. <h3>Objective</h3> To assess whether treatment with placebo for nonsevere fast-breathing pneumonia is substantively less effective than 3 days of treatment with amoxicillin. <h3>Design, Setting, and Participants</h3> This double-blind, 2-arm, randomized clinical noninferiority trial with follow-up of 14 days screened 1343 HIV-uninfected children aged 2 to 59 months with nonsevere fast-breathing pneumonia at outpatient departments of hospitals in Lilongwe, Malawi, Africa, between June 2016 and June 2017. <h3>Interventions</h3> Placebo or amoxicillin dispersible tablets administered twice daily for 3 days. <h3>Main Outcomes and Measures</h3> The primary end point was the proportion of children failing treatment by day 4 with a relative noninferiority margin of 1.5 times the failure rate in the amoxicillin group. Primary analyses were performed based on the intention-to-treat principle. Planned secondary analyses included treatment failure or relapse by day 14. <h3>Results</h3> In total, 1126 children were randomized to 3 days of amoxicillin (n = 564) or placebo (n = 562) therapy. Baseline demographic and clinical characteristics were similar between the groups. For the entire study population, the mean (SD) age was 21.3 (15.1) months, and 601 (53.4%) were female. After an interim analysis, the data safety monitoring board stopped the study because children receiving amoxicillin had a 4.0% (22 of 552 with outcome data) treatment failure rate by day 4, whereas children receiving placebo had a 7.0% (38 of 543) treatment failure rate (adjusted relative risk, 1.78; 95% CI, 1.07%-2.97%; adjusted absolute difference, 3.0%; 95% CI, 0.4%-5.7%). Among children with known day 14 outcomes, 56 of 552 (10.1%) receiving amoxicillin and 64 of 543 (11.8%) receiving placebo had either treatment failure by day 4 or relapse by day 14 (relative risk, 1.16; 95% CI, 0.83%-1.63%; absolute difference, 1.6%; 95% CI, −2.1% to 5.4%). There were no deaths. <h3>Conclusions and Relevance</h3> In HIV-uninfected children aged 2 to 59 months in a malaria-endemic region of Malawi, placebo treatment of nonsevere fast-breathing pneumonia was significantly inferior to treatment with amoxicillin. However, by day 4, approximately 93% of children receiving placebo were without treatment failure, and there was no significant difference between groups in treatment failure or relapse by day 14. The number of children with nonsevere fast-breathing pneumonia that needed amoxicillin treatment for 1 child to benefit was 33. <h3>Trial Registration</h3> ClinicalTrials.gov Identifier:NCT02760420