tbuckley/cabot-search huggingface dataset:
Abstract 13532: Diastolic Function at Presentation Has Independent Prognostic Value in Patients With Peripartum Cardiomyopathy
Authors: Antonia Delgado-Montero, Dennis McNamara, Julie B Damp, Mark Drazner, Eileen Hsich, Paul J Mather, Navin Rajagopalan, John Gorcsan
Journal: Circulation (2015)

Background: Peripartum cardiomyopathy (PPCM) is a rare disease with variable but potentially devastating consequences. The prognostic importance of alterations in LV diastolic function is unclear. Methods: Pregnancy Associated Cardiomyopathy cohort was a prospective study of 100 PPCM women from 30 centers presenting with LV ejection fraction (EF) &lt; 45% within 2 months of delivery. Baseline data were mitral inflow E-wave, A-wave, E/A ratio, E deceleration time (DT), tissue Doppler septal and lateral annular velocities and biplane LA volume index. There were 90 PPCM patients and 21 female controls (8 healthy postpartum and 13 non-pregnant) with diastolic data. LV recovery was defined as LVEF ≥ 50% at 1 year. Outcome events were predefined as death, heart transplant or LV assist device (LVAD). Results: PPCM patients were aged 30±6 years with EF 35±9% at presentation. At 1 year, 84 patients had follow-up data: 63 patients (75%) had LV recovery (EF ≥50%) and 11 patients (13%) had either LVEF ≤35% or a major event (4 LVADs and 2 deaths). Elevated filling pressures (E/A≥2 and DT&lt;150ms) were present in 57% at baseline and persisted in 11% at last echo, p&lt;0.0001. Abnormalities in baseline diastolic function were associated with clinical outcomes and lack of LV recovery: area under the ROC curve (AUC) for E/A 0.78, p=0.0002, AUC for DT 0.82, p&lt;0.0001, AUC for LA volume index 0.79, p&lt;0.0001. Diastolic measures were also predictive of persistent severe LV dysfunction (EF ≤35%) or unfavorable events: E/A, p&lt;0.0001; DT, p&lt;0.0001, and LA volume index, p=0.0001. By multivariate analysis, baseline diastolic function was independently associated with subsequent lack of LV recovery or unfavorable events (Table). Conclusions: In PPCM patients, echo-Doppler measures of diastolic function at presentation provide important prognostic information regarding LV recovery and clinical outcomes.
Updated results of a phase I study of low dose decitabine and valproic acid (VA) in patients with acute myeloid leukemia (AML): Gene reexpression, demethylation, and clinical response
Authors: R. B. Klisovic, W. Blum, B. Hackanson, C. Kefauver, S. Liu, Z. Liu, K. K. Chan, C. Plass, M. R. Grever, J. C. Byrd, G. Marcucci
Journal: Journal of Clinical Oncology (2006)

6515 Background: Decitabine, an inhibitor of DNA methyltransferase (DNMT) enzymes, has activity in myeloid malignancies at doses &gt;1 log below the MTD of 2250mg/m 2 /course which may be optimal for DNA demethylation and minimize cytotoxicity. Methods: We designed a two step trial for AML patients (pts) to determine: Step 1, the lowest dose of decitabine to induce 100% increase in or re-expression of epigenetically silenced genes in 5/6 pts treated at a dose level; and Step 2, the MTD of the histone deacetylase (HDAC) inhibitor VA given with this dose of decitabine, and whether this MTD or a lower dose leads to 90% decrease in HDAC activity. Results: Decitabine was administered to 17 pts at two dose levels. Pts had relapsed/refractory AML (N=10) or age&gt;60 and ineligible/refused standard therapy (N=7) and ranged in age from 36–83 years. Pts received decitabine at 15–20mg/m 2 /IV over 1 hr daily for 10 days (d) (3 pts also had VA 15mg/kg on days 5–21), every 28 d. Mean plasma decitabine Cmax (by a validated LC-MS/MS method) was 93 ng/ml (N=7). 10/13 pts had at least 100% increase in expression of p15 or estrogen receptor (ER, including 5/6 given 20mg/m 2 /d decitabine alone), and all 10 had clinical response. Of the 3 pts who did not have increased gene expression none responded. Western blotting showed depletion of DNMT protein in 4/6 pts. Bisulfite sequencing of the promoter region of ER confirmed that decitabine induced &gt;50% decrease in methylation in the only pt yet examined (p&lt;0.001). 9/14 pts had decrease in global DNA methylation as measured by LC-MS/MS. 10/15 pts had clinical benefit: 6 pts had clinical response, 2 with CR (1 with t-AML) and 4 with CRi (1 with a 20yr history of P. vera); 4 pts had clinical improvement-1 met all CR criteria except for BM disease by flow, 1 had platelet &gt;100K, 2 had stabilization of disease for 4–6 months. Conclusions: We demonstrated clinical activity of low dose decitabine associated with decreased levels of the DNMT1 target and increased or re-expression of epigenetically silenced genes. Combination of decitabine at 20mg/m 2 /d with VA (Step 2) has begun; complete clinical results, gene re-expression/ demethylation, and histone deacetylation data will be presented. (NCI U01 CA 76576–05) [Table: see text]
A painful wrist after a fall
Authors: Yong-Hai Zhou, Wei Wang, Ming-Hua Zheng
Journal: BMJ (2017)

A 13 year old boy presented to the orthopaedic clinic for a painful wrist after a fall forward. On examination, he had a swollen painful right wrist and no limb deformities could be found. Anteroposterior and lateral radiography for the wrist was taken (fig 1⇓). What is the diagnosis?



Fig 1  (a) Anteroposterior and …
Correction: An A13 Repeat within the 3′-Untranslated Region of Epidermal Growth Factor Receptor (EGFR) Is Frequently Mutated in Microsatellite Instability Colon Cancers and Is Associated with Increased EGFR Expression
Journal: Cancer Research (2010)

In this article (Cancer Res 2009;69:7811–8), which was published in the October 1, 2009 issue of Cancer Research (1), the Dld-1 cell line is mistakenly listed in Fig. 4 as EGFR 3′UTR mutant. This cell line is in fact EGFR 3′UTR WT.
Never let it go: Stopping key mechanisms underlying metastasis to fight pancreatic cancer
Authors: E. Giovannetti, C.L. van der Borden, A.E. Frampton, A. Ali, O. Firuzi, G.J. Peters
Journal: Seminars in Cancer Biology (2017)

Pancreatic ductal adenocarcinoma (PDAC) is an extremely aggressive neoplasm, predicted to become the second leading cause of cancer-related deaths before 2030. This dismal trend is mainly due to lack of effective treatments against its metastatic behavior. Therefore, a better understanding of the key mechanisms underlying metastasis should provide new opportunities for therapeutic purposes. Genomic analyses revealed that aberrations that fuel PDAC tumorigenesis and progression, such as SMAD4 loss, are also implicated in metastasis. Recently, microRNAs have been shown to play a regulatory role in the metastatic behavior of many tumors, including PDAC. In particular, miR-10 and miR-21 have appeared as master regulators of the metastatic program, while members of the miR-200 family are involved in the epithelial-to-mesenchymal switch, favoring cell migration and invasiveness. Several studies have also found a close relationship between cancer stem cells (CSCs) and biological features of metastasis, and the CSC markers ALDH1, ABCG2 and c-Met are expressed at high levels in metastatic PDAC cells. Emerging evidence reveals that exosomes are involved in the modulation of the tumor microenvironment and can initiate PDAC pre-metastatic niche formation in the liver and lungs. In this review, we provide an overview of the role of all these pivotal factors in the metastatic behavior of PDAC, and discuss their potential exploitation in the clinic to improve current therapeutics and identify new drug targets.
Abstract 97: Epigenetic Signatures Contribute to the Superior Endothelial Cell Identity in Human Induced Pluripotent Stem Cells Derived From Endothelial Cells
Authors: Mingtao Zhao, Shijun Hu, Rajini Srinivasan, Fereshteh Jahaniani, Ning-Yi Shao, David Knowles, Won Hee Lee, Tomek Swigut, Joanna Wysocka, Michael Snyder, Joseph Wu
Journal: Circulation Research (2015)

Human induced pluripotent stem cells (iPSCs) can be derived from multiple types of somatic cells by transient overexpression of four Yamanaka factors. Epigenetic memory of the tissue of origin is seen in early passage iPSCs, which may interfere the directed differentiation towards target lineages in disease modeling and drug discovery. Here we derived human iPSC from three types of somatic cells of the same individuals: fibroblast (FB-iPSCs), endothelial cells (EC-iPSCs) and cardiac progenitor cells (CPC-iPSCs). We then differentiated them into endothelial cells by using sequential administration of Activin, BMP4, bFGF and vEGF. EC-iPSCs show higher EC differentiation propensity and EC-specific markers (PECAM1 and NOS3) gene expression in early passage iPSCs than FB-iPSCs and CPC-iPSCs. In vivo, EC-iPSC-ECs display significantly greater revascularization capacity than those of FB-iPSCs and CPC-iPSCs when transplanted to the hindlimb ischemic mice. In addition, transplanted EC-iPSC-ECs were recovered with a higher percentage of CD31+ population and higher EC-specific markers (PECAM1, KDR and ICAM) gene expression by using single cell qPCR. In vitro, EC-iPSC-ECs exhibit better endothelial cell character maintenance along with extensive culturing and passaging. Several chromatin signatures, including H3K27ac, H3K4me1 and p300 were found highly enriched in ECs and EC-iPSCs, but not in human embryonic stem cells (ESCs). Gene ontology analysis indicates that the differentially enriched regions are primarily associated with angiogenesis and vascular development, reflecting the residual epigenetic signatures in EC-iPSCs. Finally EC-specific enhancer markers undergo dynamic changes during the process of EC fate commitment and differentiation, though the majority of them sustain conserved pattern in EC-iPSCs, CPC-iPSCs and FB-iPSCs. In conclusion, these results highlight that the residual epigenetic signatures of tissue of origin may affect lineage differentiation propensity in early-passage human iPSCs.
First-in-human dose-escalating trial of <i>E.coli</i> purine nucleoside phosphorylase and fludarabine gene therapy for advanced solid tumors.
Authors: Thomas Kenwise Chung, Eben Rosenthal, William B Parker, Paula Allan, Lisa Clemons, Deborah Lowman, Jeong Hong, Frank R Hunt, Joshua Richman, Robert Martin Conry, Kyle Mannion, William Carroll, Lisle Nabell, Eric J Sorscher
Journal: Journal of Clinical Oncology (2015)

3084 Background: The use of E. coli purine nucleoside phosphorylase (PNP) to activate fludarabine was safe and demonstrated robust antitumor activity in preclinical studies. The regimen demonstrated cytotoxicity within neighboring tumor cells that did not incorporate PNP, an effect known as bystander killing. Given the potential of this novel therapeutic, the FDA approved this clinical trial. Methods: A first-in-human multi-site Phase I clinical trial (NCT 01310179; IND 14271) was initiated to evaluate the safety and efficacy of intratumoral administration of a replication-deficient adenoviral vector expressing E. coli PNP in combination with intravenous fludarabine. Escalating doses of fludarabine comprised the first three cohorts (15, 45, and 75 mg/m2) and escalating virus in the fourth (1012 versus 1011 viral particles) with 75 mg/m2 fludarabine. Primary endpoints included adverse event rates and tumor volume change from baseline to final measurement on day 56. Results: All 12 study subjects completed therapy without any dose limiting toxicities. Change in tumor size from baseline to final measurement demonstrated a dose-dependent response, with 5 of 6 patients in Cohorts 3 and 4 achieving tumor regression compared to 0 of 6 patients in Cohorts 1 and 2 (p = 0.018). The overall adverse event rate was not dose-dependent. Most common adverse events included pain at the viral injection site (92%), drainage/itching/burning (50%), fatigue (50%), and fever/chills/flu-like symptoms (42%). Four patients experienced decreased peripheral blood counts and three patients experienced transient liver enzyme elevations that resolved spontaneously. Analysis of serum confirmed lack of systemic exposure to fluoroadenine, the active agent generated by E. coli PNP. Antibody response to adenovirus was detected in 2 patients, suggesting that neutralizing immune response is not a barrier to efficacy. Conclusions: This first-in-human clinical trial found that localized generation of fluoroadenine within tumor tissues using E. coli PNP and fludarabine is safe and effective. The pronounced effect on tumor volume after a single treatment cycle suggests phase II studies are warranted. Clinical trial information: NCT01310179.
Management of <i>Helicobacter pylori</i> Infection
Authors: Robert T. Kavitt, Adam S. Cifu
Journal: JAMA (2017)

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
Potential Number of Organ Donors After Euthanasia in Belgium
Authors: Jan Bollen, Tim van Smaalen, Rankie ten Hoopen, Ernst van Heurn, Dirk Ysebaert, Walther van Mook
Journal: JAMA (2017)

Potential Number of Organ Donors After Euthanasia in BelgiumOrgan donation after euthanasia involves patients whose request to undergo euthanasia has been granted and who voluntarily want to donate their organs after death.It requires patients to undergo euthanasia in the hospital, and organ donation is performed after circulatory death.The practice is controversial and currently only allowed in Belgium and the Netherlands.Even in these countries, it is rarely performed; as of August 2016, 43 patients undergoing euthanasia had donated organs. 1 Organ donation after euthanasia has been described in a practical manual, which addresses the medical, ethical, and legal aspects of performing euthanasia and donation after circulatory death. 2 Donation after euthanasia could potentially help ease the shortage of organs for transplantation.It is unknown how many of these patients would be medically suitable to donate organs. 3 We examined the number of patients undergoing euthanasia in Belgium who could potentially donate at least 1 organ.
Estimated Cost of Emergency Sunburn Visits—Validation of <i>ICD-9-CM</i> Search Criteria—Reply
Authors: Gery P. Guy, Zahava Berkowitz, Meg Watson
Journal: JAMA Dermatology (2017)

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 Dermatology 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 Dermatology journal
TCTAP A-044 Is Drug-eluting Balloon Highly Favorable in De Novo Coronary Lesions
Authors: Yeo-Jeong Song, Sang-Yong Yoo, Won-Kyung Lee, Woo-Dae Bang, Sang Jin Ha, Suk Min Seo, Sangsig Cheong
Journal: Journal of the American College of Cardiology (2017)
Genome-to-genome analysis highlights the effect of the human innate and adaptive immune systems on the hepatitis C virus
Authors: M Azim Ansari, Vincent Pedergnana, Camilla L C Ip, Andrea Magri, Annette von Delft, David Bonsall, Nimisha Chaturvedi, Istvan Bartha, David Smith, George Nicholson, Gilean Mcvean, Amy Trebes, Paolo Piazza, Jacques Fellay, Graham Cooke, Graham Foster, Emma Hudson, John Mclauchlan, Peter Simmonds, Rory Bowden, Paul Klenerman, Eleanor Barnes, Chris Spencer, Stop-Hcv Consortium
Journal: Nature Genetics (2017)
Oesophageal involvement in 26 consecutive patients with mucous membrane pemphigoid
Authors: O. Zehou, J.-J. Raynaud, C. Le Roux-Villet, M. Alexandre, G. Airinei, F. Pascal, M. Heller, N. Lièvre, L. Laroche, F. Caux, R. Benamouzig, C. Prost-Squarcioni
Journal: British Journal of Dermatology (2017)

Oesophageal involvement of mucous membrane pemphigoid (MMP) has not yet been thoroughly described.To characterize systematically the endoscopic lesions of a series of patients with oesophageal symptoms seen at a referral centre for autoimmune bullous diseases.Clinical, endoscopic and immunological findings of consecutively referred patients with MMP with oesophageal involvement, systemic and endoscopic treatments, and follow-up are described.Of 477 consecutive patients with MMP consulting between 2002 and 2012, 26 (5·4%) had symptomatic oesophageal involvement. Dysphagia, observed in 23 (88%) patients, was the most frequent symptom. Oesophageal symptoms could be the first sign of MMP. Patients with oesophageal involvement had a mean of three other involved sites. At initial oesophageal endoscopy, 17 of 26 patients had active lesions (intact bullae, erosions and/or erythema), 15 had stricture(s) and 12 had other cicatricial lesions. Systemic therapy alone achieved oesophageal symptom relief for five patients. Dilatation was combined with systemic therapy for 12 patients and was successful in nine; one perforation occurred.Symptomatic oesophageal involvement affected 5·4% of patients with MMP. Dermatologists and gastroenterologists should be aware of these mucocutaneous diseases and their oesophageal involvement, as it could lead to earlier diagnosis and better care. Oesophageal dilatation could be a therapeutic option for symptomatic stricture not relieved by optimized systemic therapy alone.
Effect of exercise on cancer-associated cognitive dysfunction: A proof-of-concept randomized controlled trial.
Authors: Kristin Campbell
Journal: Journal of Clinical Oncology (2014)

9583 Background: Changes in cognitive function are reported in 15-75% of individuals during or following cancer treatment. Currently, there is little available evidence of effective intervention strategies to address this issue. However, exercise presents a potentially effective intervention, as improvements in cognitive function with exercise have been demonstrated in other populations. However, to date there have been no published randomized controlled trials examining the effect of exercise on cognitive function in cancer survivors. Methods: A proof-of-concept randomized controlled trial (RCT) in women, treated for breast cancer within the past 3 years, who self-report persistent cognitive dysfunction following chemotherapy treatment (n=20). Participants were randomized to a 24-week aerobic exercise intervention or delayed exercise control. The primary outcome was self-reported cognitive function and impact on quality of life (QoL), using the FACT-CoG. The secondary outcome was performance on a standard neuropsychological test battery. Results: Compared to the control group, the exercise group had improvements in the Impact on QoL subscale (+2.9, 95% CI -0.3 to 6.0, p=0.07) and Comments of Others subscale (+1.4, 95% CI -0.9 to 3.6, p=.20) of the FACT-Cog. The exercise group also had improvements in verbal fluency, using the animal naming (5.7, 95% CI 1.8 to 9.6, p=<0.01) and motor processing speed, using Trail Making A (-12.2 seconds, 95% CI -51.1 to 26.7, p<0.01), while a reduction in time to complete Trail Making B did not reach statistical significance (-12.2 seconds, 95% CI -51.1 to 26.7, p=0.51). Conclusions: The results from this proof of concept RCT demonstrate the potential of exercise to improve self-reported symptoms cancer associated cognitive dysfunction and neuropsychological test performance in areas of verbal fluency and motor processing speed. The point estimates and variance provided by this proof-of-concept trial will serve to inform the development of a future, definitive, multi-site RCT.
Temozolomide (TMZ) for 21/28 days in patients with progressive glioblastoma (GBM): Preliminary results of phase 2 study of GICNO (Italian Neuro-Oncology Group).
Authors: A. Brandes, G. Cavallo, A. Tosoni, M. Ermani, L. Scopece, E. Franceschi, L. Nicolardi, A. Talacchi, V. Blatt, L. Crino
Journal: Neuro-Oncology (2005)
Methotrexate Therapy for Squamous Cell Carcinomas of the Head and Neck
Authors: Montague Lane
Journal: JAMA (1968)

Fourteen of 27 patients with advanced squamous cell carcinomas of the head and neck had objective responses to single, intravenous doses of methotrexate sodium, 20 to 50 mg given every 4 to 7 days. The median duration of response was 92 days. Four patients had complete remissions. Four patients did not have toxic reactions. Signs of toxicity in oral mucous membranes occurred in 12 of 14 responders and in 8 of 13 nonresponders. Moderate hematologic changes occurred in four responders and in one nonresponder. Severe hematologic signs of toxicity developed in one responder and in five nonresponders. One nonresponder died of drug toxicity. This regimen of methotrexate administration appears to be a practical and moderately effective treatment for the management of patients with advanced squamous cell carcinoma of the head and neck.
CHANGES IN FOLLOW-UP LEFT VENTRICULAR EJECTION FRACTION ASSOCIATED WITH OUTCOMES IN PRIMARY PREVENTION ICD RECIPIENTS
Authors: Yiyi Zhang, Eliseo Guallar, Elena Blasco-Colmenares, Victor Nauffal, Joseph Marine, Zayd Eldadah, Timm Dickfeld, Kenneth Ellenbogen, Gordon Tomaselli, Alan Cheng
Journal: Journal of the American College of Cardiology (2015)