tbuckley/cabot-search huggingface dataset:
First-in-human trial of microRNA cancer therapy with MRX34, a liposomal miR-34 mimic: Phase Ia expansion in patients with advanced solid tumors.
Authors: Muhammad Shaalan Beg, David S. Hong, Jasgit C. Sachdev, Andrew Jacob Brenner, Mitesh J. Borad, Ho Yeong Lim, Tae-You Kim, Carlos Becerra, Keunchil Park, Andreas G. Bader, Jay Stoudemire, Susan Smith, Sinil Kim, Yoon-Koo Kang
Journal: Journal of Clinical Oncology (2016)

TPS2597 Background: MicroRNAs (miRNAs) are naturally occurring, short (~22 nucleotides), non-coding single-stranded RNAs that comprise a new class of post-transcriptional regulators of gene expression. Each miRNA modulates the expression of hundreds of genes across distinct cellular pathways. This broad activity gives miRNA-based therapy the potential to simultaneously repress multiple oncogenic processes in the tumor microenvironment, including growth and proliferation, resistance, cancer stem cells, metastasis, and immune evasion. The tumor suppressor miRNA miR-34a has been shown to down-regulate expression of > 30 oncogenes (eg, MET, MEK1, PDGFR-α, CDK4/6, BCL2, WNT 1/3, NOTCH1, CD44), as well as genes involved in tumor immune evasion (eg, PD-L1, DGKζ). MRX34, a liposome-encapsulated miR-34a mimic, is a potential first-in-class miRNA therapy for cancer. Methods: The initial standard 3x3 dose-escalation portion of this trial (NCT01829971) is complete; here we describe the on-going phase Ia expansion in which 21 of ~80–100 planned patients have been enrolled. Eligible patients are ≥ 18 yrs, have refractory advanced solid tumors including HCC (Child-Pugh A only), RCC, melanoma, lung cancer (NSC or SC), or other solid tumors of potential interest, ECOG PS 0–2, acceptable hepatic, renal, and hematologic function, and anticipated life expectancy of > 3 m. Under required steroid premedication, MRX34 is given at the previously determined MTDs of 70 mg/m2 for HCC or 93 mg/m2 for non-HCC solid tumors in daily IV infusions for 5 consecutive days in week 1 with 2-weeks rest on a 21-day cycle (QDx5 schedule). The primary objective is safety of the recommended phase II dose (RP2D); secondary objectives are PK and biological and clinical activity. AEs are evaluated and recorded at each patient visit; antitumor activity is assessed by CT or MRI at screening, the end of cycle 2, and every even cycle thereafter. Down-regulation of cancer oncogenes, miRNA levels, and other potential pharmacodynamic markers are being evaluated, including with qRT-PCR and next-generation sequencing (NGS) analyses of white blood cells from blood samples and, as available, tumor and tissue biopsies. Clinical trial information: NCT01829971.
Association of Hospitalist Years of Experience With Mortality in the Hospitalized Medicare Population
Authors: James S. Goodwin, Habeeb Salameh, Jie Zhou, Siddhartha Singh, Yong-Fang Kuo, Ann B. Nattinger
Journal: JAMA Internal Medicine (2017)

Substantial numbers of hospitalists are fresh graduates of residency training programs. Current data about the effect of hospitalist years of experience on patient outcomes are lacking.To describe the association of hospitalist years of experience with 30-day mortality and hospital mortality of their patients.We used a 5% sample of national Medicare data of patient and hospital characteristics to build a multilevel logistic regression model to predict mortality as a function of years of experience of the hospitalists. We created 2 cohorts. The first was a cross-sectional cohort of 21 612 hospitalists working between July 1, 2013, and June 30, 2014, with a 5-year look-back period to assess their years of prior experience as a hospitalist, and the second was a longitudinal cohort of 3860 hospitalists in their first year of practice between July 1, 2008, and June 30, 2011, who continued practicing hospital medicine for at least 4 years.Thirty-day postadmission mortality adjusted for patient and hospital characteristics in a 3-level logistic regression model. Hospital mortality was a secondary outcome.Among 21 612 hospitalists caring for Medicare inpatients from July 1, 2013, to June 30, 2014, 5445 (25%) had 1 year of experience or less, while 11 596 (54%) had 4 years of experience or more. We then identified 3860 physicians in their first year as hospitalists who continued to practice as hospitalists for 4 years. There was a significant association between hospitalist experience and mortality. Observed 30-day mortality was 10.50% for patients of first-year hospitalists vs 9.97% for patients of hospitalists in their second year. The mortality odds for patients of second-year hospitalists were 0.90 (95% CI, 0.84-0.96) compared with patients of first-year hospitalists. Observed hospital mortality was 3.33% for patients cared for by first-year hospitalists vs 2.96% for second-year hospitalists. (odds ratio, 0.84; 95% CI, 0.75-0.95). For both 30-day and hospital mortality, there was little change in odds of mortality between the second year and subsequent years of experience.Patients cared for by hospitalists in their first year of practice experience higher mortality. Early-career hospitalists may require additional support to ensure optimal outcomes for their patients.
Microphysiological Analysis Platform of Pancreatic Islet β‐Cell Spheroids
Authors: Sang Hun Lee, SoonGweon Hong, Jihwan Song, Byungrae Cho, Esther J. Han, Sravani Kondapavulur, Dongchoul Kim, Luke P. Lee
Journal: Advanced Healthcare Materials (2017)

Abstract The hallmarks of diabetics are insufficient secretion of insulin and dysregulation of glucagon. It is critical to understand release mechanisms of insulin, glucagon, and other hormones from the islets of Langerhans. In spite of remarkable advancements in diabetes research and practice, robust and reproducible models that can measure pancreatic β‐cell function are lacking. Here, a microphysiological analysis platform (MAP) that allows the uniform 3D spheroid formation of pancreatic β‐cell islets, large‐scale morphological phenotyping, and gene expression mapping of chronic glycemia and lipidemia development is reported. The MAP enables the scaffold‐free formation of densely packed β‐cell spheroids (i.e., multiple array of 110 bioreactors) surrounded with a perfusion flow network inspired by physiologically relevant microenvironment. The MAP permits dynamic perturbations on the β‐cell spheroids and the precise controls of glycemia and lipidemia, which allow us to confirm that cellular apoptosis in the β‐cell spheroid under hyperglycemia and hyperlipidemia is mostly dependent to a reactive oxygen species‐induced caspase‐mediated pathway. The β‐cells' MAP might provide a potential new map in the pathophysiological mechanisms of β cells.
Abstract 17368: Long-Term Arrhythmic Outcome of Non-Ischemic Dilated Cardiomyopathy: Prognostic Value of Contrast-Enhanced Cardiac Magnetic Resonance
Authors: Martina Perazzolo Marra, Manuel De Lazzari, Alessandro Zorzi, Francesco Corbetti, Francesco Tona, Giulia Vettor, Federico Migliore, Cristina Basso, Sabino Iliceto, Domenico Corrado
Journal: Circulation (2012)

Purpose:  Although risk stratification for cardiac sudden death in non-ischemic dilated cardiomyopathy (DCM) relies on left ventricular (LV) dysfunction, predictors indicating the myocardial substrates of tissue heterogeneity causing arrhythmias in DCM remain to be established. The aim of the present study was to asses the role of presence and amount of late gadolinium enhancement (LGE) as detected by contrast-enhanced cardiac magnetic resonance (CE-CMR) for arrhythmic stratification in patients with non-ischemic DCM.   Methods:  136 consecutive patients (108 males, 79.4%; mean age 48.7±15 years) with non-ischemic DCM (EF ≤ 50%) were prospectively enrolled. All patients underwent initial CE-CMR and were followed for the primary end point of sustained ventricular tachycardia (SVT), and for the composite end-point of SVT, appropriate ICD intervention and sudden cardiac death (SCD) for a mean follow-up of 52±37 months. For each patient the LGE was classified as absent, gray, midwall/subepicadial stria and patchy and quantified as percentage of LV mass.   Results:  LGE was identified in 88 patients (65%) and affected 6.3%±8.8% (median value 4.5%) of LV wall. A gray pattern was observed in 13 (14.8%), a stria in 65 (73.8%), a septal junction in 35 (39.8%), a patchy pattern in 4 (4.5%). During the follow-up, 58/111 patients (42.6%) experienced adverse events, such as sustained VT (n=18), SCD (n=8), appropriate ICD interventions (n=12). On univariate analysis, the CE-CMR variables significantly associated with arrhythmic composite end point were the presence of LGE (HR 2.34; 95% CI 1.27-4.29, p    Conclusions:  In patients with DCM, LV myocardial scar measured by LGE on CE-CMR, is an independent predictor of adverse outcome and may contribute to assess the arrhythmogenic risk and to identify candidates for ICD therapy regardless EF.
Дисбаланс калікреїн-кінінової системи при хронічному панкреатиті у поєднанні з ожирінням і результати його комплексної корекції
Authors: L.S. Babinets, K.Yu. Kytsai
Journal: GASTROENTEROLOGY (2017)

Актуальність. Значна роль у виникненні та прогресуванні хронічного панкреатиту, одного з найбільш поширених захворювань у загальнотерапевтичній практиці, належить активації калікреїн-кінінової системи (ККС), яка бере участь у процесах розвитку запалення, згортання крові та фібринолізу, в імунних реакціях, формуванні больового синдрому та ін. Мета. Дослідження динаміки показників ККС при застосуванні препарату метадоксин у складі комплексної терапії хворих на хронічний біліарний панкреатит (ХБП) у поєднанні з ожирінням. Матеріали та методи. Досліджено 75 хворих на ХБП у поєднанні з ожирінням. Хворих було розподілено на 2 групи. Перша група (30 осіб) отримувала загальноприйняте лікування (ЗПЛ). Друга група (45 осіб) отримувала в комплексі до ЗПЛ препарат метадоксин. Результати. Після проведеного лікування позитивна динаміка спостерігалась в обох групах. Проте у пацієнтів другої групи простежувалась більш значуща позитивна динаміка показників ККС: рівень протеолітичної активності знизився на 9,0 %, калікреїну — на 20,0 %, a1-інгібітор протеїназ — на 7,2 %, а показник прекалікреїну зріс на 6,4 %, a2-макроглобулін — на 10,8 %, кініназа II — на 10,7 % у порівнянні з 1 групою. Висновки. Застосування метадоксину у складі комплексної терапії хворих на ХБП із коморбідним ожирінням сприяло вірогідному підвищенню ефективності ЗПЛ.
A Woman in Her Late 50s With Palpitations and Light-headedness
Authors: Ahmed M. S. E. K. Abdelaty, Simon L. Hetherington, Eylem Levelt
Journal: JAMA Cardiology (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 Cardiology 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 Cardiology journal
Point mutation in p14ARF-specific exon 1β of <i>CDKN2A</i> causing familial melanoma and astrocytoma
Authors: A. M. McInerney-Leo, L. Wheeler, R.A. Sturm, J.-M. Tan, J.E. Harris, L. Anderson, K. Jagirdar, M.A. Brown, P.J. Leo, H.P. Soyer, E.L. Duncan
Journal: British Journal of Dermatology (2017)
The Landscape of Actionable Genomic Alterations in Cell-Free Circulating Tumor DNA from 21,807 Advanced Cancer Patients
Authors: Oliver A. Zill, Kimberly C. Banks, Stephen R. Fairclough, Stefanie A. Mortimer, James V. Vowles, Reza Mokhtari, David R. Gandara, Philip C. Mack, Justin I. Odegaard, Rebecca J. Nagy, Arthur M. Baca, Helmy Eltoukhy, Darya I. Chudova, Richard B. Lanman, AmirAli Talasaz
Journal: Clinical Cancer Research (2018)

Abstract Purpose: Cell-free DNA (cfDNA) sequencing provides a noninvasive method for obtaining actionable genomic information to guide personalized cancer treatment, but the presence of multiple alterations in circulation related to treatment and tumor heterogeneity complicate the interpretation of the observed variants. Experimental Design: We describe the somatic mutation landscape of 70 cancer genes from cfDNA deep-sequencing analysis of 21,807 patients with treated, late-stage cancers across &amp;gt;50 cancer types. To facilitate interpretation of the genomic complexity of circulating tumor DNA in advanced, treated cancer patients, we developed methods to identify cfDNA copy-number driver alterations and cfDNA clonality. Results: Patterns and prevalence of cfDNA alterations in major driver genes for non–small cell lung, breast, and colorectal cancer largely recapitulated those from tumor tissue sequencing compendia (The Cancer Genome Atlas and COSMIC; r = 0.90–0.99), with the principal differences in alteration prevalence being due to patient treatment. This highly sensitive cfDNA sequencing assay revealed numerous subclonal tumor-derived alterations, expected as a result of clonal evolution, but leading to an apparent departure from mutual exclusivity in treatment-naïve tumors. Upon applying novel cfDNA clonality and copy-number driver identification methods, robust mutual exclusivity was observed among predicted truncal driver cfDNA alterations (FDR = 5 × 10−7 for EGFR and ERBB2), in effect distinguishing tumor-initiating alterations from secondary alterations. Treatment-associated resistance, including both novel alterations and parallel evolution, was common in the cfDNA cohort and was enriched in patients with targetable driver alterations (&amp;gt;18.6% patients). Conclusions: Together, these retrospective analyses of a large cfDNA sequencing data set reveal subclonal structures and emerging resistance in advanced solid tumors. Clin Cancer Res; 24(15); 3528–38. ©2018 AACR.
EphA2 gene targeting using neutral liposomal small interfering RNA (EPHARNA) delivery: A phase I clinical trial.
Authors: Aung Naing, Gabriel Lopez-Berestein, Siqing Fu, Apostolia Maria Tsimberidou, Shubham Pant, Sarina Anne Piha-Paul, Filip Janku, David S. Hong, Selma Sulovic, Xialong Meng, Amir A. Jazaeri, Chaan S. Ng, Daniel D. Karp, Vivek Subbiah, Funda Meric-Bernstam, Rahul Mitra, Sherry Wu, Anil Sood, Robert L. Coleman
Journal: Journal of Clinical Oncology (2017)

TPS2604 Background: EphA2 is a member of the largest subfamily of receptor tyrosine kinases, with over 14 receptors and 8 ligands. EphA2 overexpression is common in many human cancers, including lung, breast, prostate, colorectal, pancreatic, melanoma, esophageal and endometrial cancers. EphA2 can function as an oncoprotein when introduced into cells with low expression. In addition, downregulation of constitutive expression reduces tumorigenicity in breast, endometrial, ovarian and pancreatic cancers in vitro and in vivo models. EphA2 is a desirable target because of its selective expression in cancer (vs. adult normal tissue), and its important role in promoting tumor growth and metastasis. It has kinase-dependent and independent functions, making it an ideal target for RNAi-based targeting. We have previously reported that EphA2 siRNA incorporated in DOPC nanoliposomes (EPHARNA) was highly effective in reducing EphA2 protein levels after a single dose. In addition, three weeks of treatment with EPHARNA (150 μg/kg twice weekly) in an orthotopic mouse model of ovarian cancer (HeyA8 or SKOV3ip1) significantly reduced tumor growth compared with non-silencing siRNA, and demonstrated synergistic anti-tumor activity when combined with conventional chemotherapy. EPHARNA underwent GLP development in 2 animal models (murine and primate) at M.D. Anderson to support the IND (#72924). The first-in-human trial (NCT01591356) is ongoing and recruiting study subjects. Methods: Adult Patients &gt; 18 years of age with histologic proof of advanced recurrent solid tumors, who are not candidates for known regimens or protocol treatments of higher efficacy or priority. All patients (dose escalation and dose expansion phases) must be willing to undergo pre- and post-treatment biopsies. For dose expansion phase, patients must have EphA2 overexpression by IHC evaluation. Enrollment is ongoing for the dose escalation with the plan for dose expansion. A total of 16 patients have been enrolled and treated in the dose escalation phase. Clinical trial information: NCT01591356.
Treatment of Immune Thrombocytopenia
Authors: Heather R. Wolfe, Mishi Bhushan, Sung-hee Choi
Journal: JAMA Internal Medicine (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 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 15804: Utility of Multi-modal Imaging in the Diagnosis of Pulmonary Valve Endocarditis
Authors: Jennifer S Li, Kevin D Hill, Christoph P Hornik, Richard A Krasuski, Piers C Barker, Robert D Jaquiss, Michael J Campbell
Journal: Circulation (2016)

Introduction:  Definitive echocardiographic evidence is a major criterion for the diagnosis of infective endocarditis by modified Duke Criteria. Pulmonary valve infectious endocarditis (PVIE), however, can be challenging to identify by echo. We sought to evaluate the added utility of multimodal imaging in PVIE.   Methods:  We retrospectively analyzed demographic, laboratory, imaging, clinical, and surgical data from patients diagnosed with PVIE (2008-2015). All patients had undergone TEE as well as cardiac MRI or PET/CT and had Duke major and minor criteria evaluated.   Results:  A total of 17 patients were identified with definite PVIE (76 % male and ages 4-70 years). Fourteen patients had congenital heart disease with RV to PA conduits; 3 with subsequent transcatheter pulmonary valve implant. Overall, 15/17 (88%) had positive blood cultures: strep spp 6, staph spp 5, HACEK spp 3, enterococcus 1. Only 9/ 17 demonstrated TEE evidence of PVIE. In 8 cases, TEE was negative but showed new PV obstruction and evidence of PVIE was subsequently seen by PET/CT (n=5; see figure, arrow denotes area of abnormality) or cardiac MRI (n=3). Multimodal imaging was significantly better than TEE alone for detection of PVIE (17/17 versus 9/17, p=0.001). PVIE was confirmed by surgery in 14 cases.   Conclusion:  The ability to detect endocardial involvement in PVIE by echocardiography is poor, but echo is helpful in identifying new obstruction. Multimodal imaging improves the ability to preoperatively identify endocardial involvement in PVIE. Consideration should be given for PVIE to revise Duke criteria to include new obstruction and endocardial involvement by multimodal imaging.
Efficacy and Safety of Olopatadine/Mometasone Combination Nasal Spray in Patients With Seasonal Allergic Rhinitis
Authors: Frank C. Hampel, Andrew J. Pedinoff, Robert L. Jacobs, Aurora Breazna, Cynthia F. Caracta, Sudeesh K. Tantry
Journal: Journal of Allergy and Clinical Immunology (2018)
Fontan-Associated Liver Disease
Authors: Curt J. Daniels, Elisa A. Bradley, Mike J. Landzberg, Jamil Aboulhosn, Robert H. Beekman, Wendy Book, Michelle Gurvitz, Anitha John, Binu John, Ariane Marelli, Bradley S. Marino, L. LuAnn Minich, John J. Poterucha, Elizabeth B. Rand, Gruschen R. Veldtman
Journal: Journal of the American College of Cardiology (2017)
Predictive factors of bevacizumab efficacy in relapsed glioblastoma patients.
Authors: Patrizia Farina, Marianne Labussiere, Giuseppe Lombardi, Anna Luisa Di Stefano, Jaime Gallego, Caroline Cheneau, Vittorina Zagonel, Marc Sanson
Journal: Journal of Clinical Oncology (2014)

2032 Background: Bevacizumab is widely used in recurrent glioblastoma patients. Despite encouraging response rate, some patients do not respond to this schedule and many develop an early relapse. Predictive biomarkers of response or resistance are thus highly desirable to improve clinical benefit. Methods: Seventy patients with recurrent glioblastoma treated with bevacizumab (40 at first recurrence, 30 at > first recurrence) were included in the cohort and sequential plasma samples were collected before and during the treatment. The plasma of 23 healthy volunteers was also collected. Plasma concentrations of VEGF, PlGF, Ang2, TEK/Tie2 receptor (sTie2), BMP9, sFlt1, sRobo4 levels were assessed by ELISA based assays. Response to treatment was evaluated according to RANO criteria. Results: Median OS was 28.4 months for responders, 19.1 months for non responders patients (p=0.0009). Median PFS was 25.4 weeks for responder patients and 10.1 weeks for non responder patients (p< 0.0001). A median of 10 cycles (range 2-32) per patient was administered. 36 patients were responders (4 complete responses and 32 partial responses) and 34 patients were considered as non responders (15 stable diseases and 19 progressive diseases). Baseline levels of VEGF-A, and PlGF were higher in patients than in healthy volunteers (p<0.0001) whereas BMP9 baseline median concentration was reduced in patients (p= 0.003), and no difference was found for Ang2, sTie2, sFlt1 and sRobo4 between patients and healthy volunteers. No biomarker at baseline was associated with response, PFS or OS. During the first two months of bevacizumab treatment, VEGF-A, sTie2, Ang2 and sRobo4 decreased whereas PlGF level strongly increased. Bevacizumab treatment did not affect plasma levels of BMP9 and sFlt1. The evolution of plasma concentrations did not discriminated responder and non responder patients. Finally we found no significant variation for any biomarker at relapse. Conclusions: Our study identified plasmatic markers associated with gliomas and level variation associated with bevacizumab treatment but failed to identify any predictor of response, PFS or OS.
Mold exposure affects the development of atopic dermatitis in early life especially in infants with epithelial dysfunction
Authors: Eun Lee, So-Yeon Lee, Ji-Sun Yoon, Hyun-ju Cho, Sungsu Jung, Si Hyeon Lee, Kangmo Ahn, Kyung Won Kim, Youn Ho Shin, Dong In Suh, Soo-Jong Hong
Journal: Journal of Allergy and Clinical Immunology (2018)