tbuckley/cabot-search huggingface dataset:
Disease and treatment characteristics of breast cancer in an urban, low-income hospital following a major hurricane: A temporal and racial analysis.
Authors: Naomi Gadinsky, Melissa Lina Keeport, Adeline Jae Hyun Shin, Sudesh Srivastav, Rebecca Kruse-Jarres
Journal: Journal of Clinical Oncology (2013)

e12503 Background: The Medical Center of Louisiana, New Orleans (MCLNO) serves a metropolitan area and is the only hospital delivering care to the indigent population in the area. Hurricane Katrina devastated New Orleans on 8/29/05. No oncology services were available for two years. We examined characteristics/care for patients with breast cancer 2 years after re-opening clinics compared with the subsequent 2.5 years. Differences between Whites (W) and African Americans (AA) were examined and compared to state and national averages. Methods: After IRB approval, we reviewed charts of patients establishing care for breast cancer at MCLNO between 09/07-05/12: Group 1 (09/07-08/09) vs. Group 2 (09/09 – 05/12). Racial analysis was done between W and AA independent of temporal factors. Results: Our cohort included 153 patients (25 W, 105 AA , and 23 other race): Group 1- 68 patients, Group 2- 85. There were no significant temporal or racial differences in age, race, insurance, menopausal status, family history, cancer type, stage, or treatment regimen. More AA were triple negative (25.5% AA, 0% W; p= 0.002). Compared to state and national averages, our patients underwent more mastectomies: 58% mastectomy (M) and 42% lumpectomy (L) - compared to Louisiana (M - 50.7%, L - 48.7%) and the National (M - 42.0%, L - 57.8%) data. Our cohort presented with more advanced disease: 10.5% presented with stage IV breast cancer, which is higher than the state average (6.0%) and the national average (5.5%). Conclusions: Despite the suspicion that tumor presentation would be worse after a delay in access to care due to Katrina and that AA might have even worse characteristics, our data showed this not to be the case. Interesting was the finding that triple negative cancers seemed to be an AA phenomenon. It is important to continue following these patients to see how these presenting and prognostic factors will affect long term patient outcomes. [Table: see text]
Chromosome 1 abnormalities and clinical outcomes in multiple myeloma in the era of novel agents.
Authors: Smith Giri, Scott F. Huntington, Rong Wang, Amer Methqal Zeidan, Nikolai Alexandrovich Podoltsev, Steven Gore, Xiaomei Ma, Cary Philip Gross, Amy J. Davidoff, Natalia Neparidze
Journal: Journal of Clinical Oncology (2019)

8044 Background: Abnormalities of chromosome 1 (C1A) are common genetic mutations in patients (pts) with Multiple Myeloma (MM). While several small studies have reported worse outcomes for C1A, the prevalence, real-world treatment and outcomes for pts with C1A are unknown. Methods: We used the Flatiron Health Electronic Health Record (EHR)-derived database to identify pts with newly diagnosed MM from 01/2011 to 03/2018 with Fluorescence In situ Hybridization (FISH) testing within 90 days of diagnosis and defined lines of therapy. We identified pts with C1A and other high-risk mutations (HRM; 17p deletion, t14;16 and t4;14). Pts were followed until 3/31/2018 or death. The primary outcome was overall survival (OS). We used Kaplan Meier methods and compared OS for pts with/without C1A using log-rank tests stratified for HRM. We used Cox regression analysis to compare OS across groups, adjusting for age, gender, performance status, stage, HRM and treatment (triple regimen vs other). Results: The total sample included 3,578 pts: median age at diagnosis was 69 yrs (IQR 31-85), with 54% males and 60% whites. IgG(57%) and IgA(22%) were the most common M-protein subtypes. At baseline, 844 (24%) had C1A. Pts with C1A had higher stage (ISS III 35% vs 26%; p &lt; 0.01) and other HRM (27% vs 14%, p &lt; 0.01). Common first line-therapies included bortezomib(V), lenalidomide(R) and dexamethasone (D) (35%), RD (20%) followed by VD(15%). Use of VRD was higher with C1A vs without (40% vs 33% respectively, p &lt; 0.01). Median OS was 66.9 months for the entire cohort and was lower for pts with C1A vs without (median OS 46.6 vs 70.1 months; log rank p &lt; 0.01). Multivariable Cox survival analysis showed that C1A was independently associated with worse OS (adjusted HR 1.64; 95% CI 1.23-2.19); p &lt; 0.01). Other predictors of worse survival included older age, black ethnicity, higher ISS stage, poor performance status and HRM. Conclusions: In this large study of real-world practice, C1A was associated with inferior OS independent of other HRM, despite higher use of VRD. Future studies are needed to assess whether specific regimens improve outcomes for C1A compared to patients without HRM.
A randomized phase II trial of CX-01 with standard therapy in elderly patients with acute myeloid leukemia (AML).
Authors: Tibor Kovacsovics, Moshe Yair Levy, Rachel J. Cook, Jonathan E. Kolitz, Peter Westervelt, William Bruce Donnellan, Robert K. Stuart, John Leonard Reagan, Michaela L. Tsai, Matthew Joseph Wieduwilt, Michael B. Maris, Don A. Stevens, Jay Yang, Cecilia Arana-Yi, Hana Safah, Stephen Garrett Marcus, Paul J. Shami
Journal: Journal of Clinical Oncology (2019)

7001 Background: Elderly AML patients have poor outcomes irrespective of therapy. CX-01 is a low anticoagulant heparin derivative that retains heparin’s ability to alter the activity of the CXCL12/CXCR4 axis, P-selectin, extracellular histones, and Platelet Factor 4. A pilot study of CX-01 combined with standard therapy for AML led to a complete remission (CR) rate of 92% ( Blood Adv 2:381, 2018). We conducted a randomized, dose-finding study of the same combination in newly diagnosed elderly AML patients. Methods: 76 fit patients older than 59 were randomized to induction with idarubicin and cytarabine on a 7+3 schedule only (Group 1); 7+3 with a lower dose of CX-01 (0.125 mg/kg/hour) (Group 2); or 7+3 with a higher dose of CX-01 (0.25 mg/kg/hour) (Group 3). Patients in CR received consolidation therapy consisting of up to 3 cycles of intermediate dose cytarabine (1000 mg/m 2 every 12 hours on Days 1, 3, 5) without or with the same dose of CX-01 for Groups 1, 2, and 3, respectively. CX-01 was given as a continuous infusion after a 4 mg/kg bolus until completion of chemotherapy. Results: 66 of 75 treated patients were evaluable for response. Ten patients were not evaluable due to withdrawal of consent (6 patients), introduction of midostaurin after its approval (3 patients), or death due to hepatic sinusoidal obstructive disease at Day 21 (1 patient in Group 2). We present results for evaluable patients and not on an intent to treat basis. Baseline characteristics were similar across groups. The composite CR rate (CR + CRi) was highest for patients in Group 3 with 89% patients achieving a composite CR as compared to 58% and 50% in Groups 1 and 2, respectively. Kaplan-Meier curves indicated a statistically significant improvement in event free survival (EFS) (P = 0.019) and a non-significant trend (P = 0.10) to improvement in OS in Group 3 as compared to Group 1. Groups 1 and 2 were comparable for EFS and OS. CX-01 was well tolerated without increased incidence of bleeding in Groups 2 and 3. Conclusions: The encouraging CR rate and EFS in elderly fit patients with newly diagnosed AML suggests that CX-01 may potentiate the efficacy of standard AML induction therapy. A randomized study to confirm these findings with the higher dose of CX-01 is warranted. Clinical trial information: NCT02873338.
Abstract 9127: C-myb-regulated Expression Of Mir-143/145 In Embryonic Stem Cell-derived And Adult Vascular Smooth Muscle Cells
Authors: Omar A El-Mounayri, Masayoshi Ishida, Mansoor Husain
Journal: Circulation (2012)

Background: The c-myb gene encodes for the transcription factor c-Myb, which has been implicated in the differentiation of vascular smooth muscle cells (VSMCs) from neural crest and embryonic stem cells (ESCs). Mouse ESCs lacking c-myb (KO) failed to express SMC-specific genes and did not differentiate into contractile SMCs in embryoid bodies (EB), with c-Myb regulating the formation of a specific Flk-1+/PDGFRα- (F+/P-) progenitor of VSMCs. Others showed that expression of the miR-143/145 cluster is restricted to adult SMC lineages and promotes the expression of contractile genes. Hypothesis: c-Myb mediates the transcriptional regulation of miR-143/145. Methods &amp;Results : Flow-sorting of cardiovascular-directed d3.75 EBs showed high levels of miR-143/145 expression in F+/P- (c-myb high) cells, with low levels in other (c-myb low: F+/P+ and F-/P+) cell populations. Importantly, no differences in the expression levels of miR-143/145 could be detected in F+/P-, F-/P+ and F+/P+ cells derived from c-myb KO EBs. Multiple putative c-Myb consensus-binding sites (conserved in human and mouse) were identified in 3kb and 20kb enhancers upstream of the miR-143/145 cluster. Chromatin immunoprecipitation assays in both cardiovascular-directed d3.75 EBs and immortalized mouse adult aortic SMCs (MOVAS) revealed c-Myb binding to multiple specific sites. Next, c-Myb responsiveness of wild-type and deletion mutant enhancer-reporter constructs was assayed in HEK293 cells. These studies confirmed two c-Myb-dependent miR-143/145 enhancer activities. Conclusion: Our data suggest that c-Myb-regulated VSMC differentiation and contractile gene expression may be mediated by direct binding to specific transcription enhancer elements in the miR-143/145 cluster. *Authors have contributed equally to this work.
Analysis of Pathologic Complete Response 10 Weeks After Radiotherapy—A Radiobiological Sin
Authors: Jing Liu, Yiyuan Zhang, Jinbo Yue
Journal: JAMA Oncology (2019)

Our website uses cookies to enhance your experience. By continuing to use our site, or clicking "Continue," you are agreeing to our Cookie Policy | Continue JAMA Oncology 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 Oncology journal
Endozepines and their receptors: Structure, functions and pathophysiological significance
Authors: Marie-Christine Tonon, Hubert Vaudry, Julien Chuquet, Florent Guillebaud, Jinjiang Fan, Olfa Masmoudi-Kouki, David Vaudry, Damien Lanfray, Fabrice Morin, Vincent Prevot, Vassilios Papadopoulos, Jean-Denis Troadec, Jérôme Leprince
Journal: Pharmacology & Therapeutics (2019)
Preclinical characterization of PF-03732010: A human IgG1 mAb against P-cadherin, reveals antitumor and antimetastatic activity in xenografts
Authors: Cathy Zhang, Zhengming Yan, Maria Arango, Ming Qiu, Pramod Mehta, Casperson Jerry, Todd VanArsdale, Gerrit Los, Kenna Anderes
Journal: Cancer Research (2008)

2575   P-cadherin is one member of the classical cadherin family and plays a critical role in tumor cell-cell and cell-stroma adhesions. Up-regulation of P-cadherin has been frequently reported in major tumors such as colon, lung, breast, pancreatic and bladder cancers. Here we report the in vivo antitumor activity of PF-03732010, a human IgG1 mAb that binds to both human and mouse P-cadherin with high affinity and selectivity. Antitumor acitivity of PF-03732010 was assessed in orthotopic or ectopic xenografts models including 1) PC-3M-luc-P-Cad 2) MDA-MB-435-luc-P-Cad subrenal capsule model (SRC) and 3) MDA-MB-435-luc-P-Cad experimental metastasis model. Surgically implanted tumor models are inaccessible to traditional caliper measurements; therefore, bioluminescence imaging (BLI) was applied to evaluate the antitumor activity of PF-03732010. PC3M-luc-PCad and MDA-MB-435-HAL-luc-PCad cells were stably transfected to constitutively express luciferase and overexpress P-Cadherin. PF-03732010 (5 and 20 mg/kg) displayed significant tumor growth inhibition (TGI) of 57% and 73% respectively in the PC3M-luc-PCad model. In addition, BLI revealed PF-03732010 at 5 and 20 mg/kg inhibited lymph node metastases. In MDA-MB-435-HAL-luc-PCad SRC model, distant metastasis in the lungs can be visualized the 4 th  week after the tumor implant. PF-03732010 (10, 20 & 40 mg/kg) showed significant antitumor activity in MDA-MB-435-HAL-luc-PCad SRC model with TGI of 51.8%, 66.5% and 68.0% respectively against the primary tumor; and antimetastatic activity of 54.2%, 72.8% and 82.2% respectively against the tumor burden in the lungs. Kaplan-Meier survival plot showed that PF-03732010 significantly improved mouse medium survival time compared to the vehicle treated group. IHC examination of MDA-MB-435-HAL-luc-PCad SRC tumors showed a dose-dependent decrease in β-actin and Ki67, suggesting antitumor activity is a result of cytoskeletal disruption and reduced proliferation due to PF-03732010 blockade of P-cadherin signaling. We further evaluated the antimetastatic activity of PF-03732010 in an experimental model of metastasis, IV delivery of MDA-MB-435-HAL-luc-PCad cells to mice. When mice were treated with PF-03732010 either twenty-four hours before or 14 days after injection of tumor cells, PF-03732010 (20 mg/kg) significantly inhibited metastases and tumor burden increase in lungs (TGI 93% and 87% respectively) with a concomitant increase in median survival of 39 and 19 days respectively. Overall, PF-03732010 consistently demonstrated significant antitumor activity, reduction in metastatic burden and improvement in survival. PF-03732010 is expected to possess antitumor activity against tumors that over-express P-cadherin and is a promising new antibody for the treatment of certain cancers.
US government treatment of migrant children held in detention condemned by eyewitnesses
Authors: Owen Dyer
Journal: BMJ (2019)

Migrant children detained by US Customs and Border Protection (CBP) are not allowed to wash, change their clothes, eat nutritious food, or sleep properly, according to lawyers who visited a facility in Clint, Texas. The eyewitnesses also reported seeing babies and toddlers being looked after by other children.

The accounts come a week after a US government attorney argued before a federal appeal court that the government has no duty to provide migrant detainee children with towels, soap, toothbrushes, or sleep.

A 1997 legal agreement in which the government promised to provide “safe and sanitary” conditions for detained children had not specified these items, justice department attorney Sarah Fabian argued.

The three appeal court judges appeared astonished by the government’s claims. “Are you really going to stand up and tell us that being able to sleep isn’t a question of safe and sanitary conditions?” …
The Medical Hospital Readmission Reduction Program
Authors: Christopher Ody, David Cutler
Journal: JAMA Internal Medicine (2019)

Our website uses cookies to enhance your experience. By continuing to use our site, or clicking "Continue," you are agreeing to our Cookie Policy | Continue JAMA 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 P112: Peripheral Arterial Disease and Carotid Atherosclerosis among Middle-aged Women Living in Chiapas, Mexico: Preliminary Results
Authors: Eduardo Ortiz-Panozo, Martin Lajous, Elsa Yunes-Díaz, Nataly Mercado, Andrea Luviano, Fernando Flores-Silva, Vidal Dircio-Delgado, Carlos Cantu-Brito, Andres Catzin-Kuhlmann, Ruy López-Ridaura
Journal: Circulation (2013)

Background: Mexico is undergoing a fast-paced epidemiological and nutritional transition. Evaluating the presence of early cardiovascular disease and understanding risk factors leading to it in this context may provide insight on prevention strategies for the growing burden of this disease in developing countries. Methods and Results: We evaluated subclinical cardiovascular disease in 443 women aged ≥40 years in an urban and a rural site in Chiapas, Mexico. All women were participants in the ongoing ESMaestras cohort, a prospective study of 116,683 Mexican female teachers, which started in 2006-2008. In September 2012, an evaluation of subclinical cardiovascular disease was undertaken in a sub-cohort of 2,000 ESMaestras participants. We present preliminary results from this initial effort. Women were invited to a clinical site where ankle-brachial index (ABI) were measured by previously standardized personnel using the automated VaSera VS-1000 sphyngmomanometer. Carotid intima-media thickness (IMT) was assessed by a neurologist. In 52 participants IMT measurements were repeated to assess the reproducibility of the measurements. Mean age was 48.1 (SD 4.2) and mean body mass index (BMI) was 28.7 kg/m2 (SD 4.7). Mean ABI was 1.06 (SD 0.09) and peripheral artery disease (ABI of &lt;0.90), was present in 4.1% of participants. Mean IMT was 0.68 mm (SD 0.08) and the prevalence of carotid atherosclerosis (IMT ≥1.2 mm) was 1.9%. The intraclass correlation to assess reproducibility of IMT measurements was 0.89 (95% confidence interval 0.82-0.94). Pearson’s correlation coefficients for IMT and BMI (n=312) and ABI and BMI (n=443) were 0.25 (p&lt;0.001) and -0.17 (p&lt;0.001), respectively. No differences were observed between the urban and rural site. Conclusions: In an initial effort to characterize subclinical cardiovascular disease we found a relatively high prevalence of peripheral arterial disease in a middle-aged population of Mexican women, underlining the increasing burden cardiovascular disease in this population.
Abstract 16788: iPSC Modeling of LMNA-associated Dilated Cardiomyopathy: The Importance of Karyotyping
Authors: Cecilia H Nguyen, Halida P Widyastuti, Linda A McCarthy, Anna Grosberg, Michael V Zaragoza
Journal: Circulation (2017)

Mutations in Lamin A/C (LMNA) manifest in a broad range of diseases including the aging disorder progeria and dilated cardiomyopathy. Although primary cardiomyocytes from affected patients are diff...
Abstract 17066: Indications for Implantable Cardioverter-Defibrillator Placement in Pediatric Patients With Hypertrophic Cardiomyopathy
Authors: Ramiro W Lizano Santamaria, Chun-Po S Fan, Kyle Runeckles, Lars Grosse-Wortmann, Elizabeth Stephenson, Lee Benson
Journal: Circulation (2018)

Background: Sudden cardiac death (SCD) is the most common cause of death in children and adolescents with hypertrophic cardiomyopathy (HCM). Implantable cardio-defibrillators (ICD) are highly effective in preventing SCD, however, indications for ICD placement in the young is mainly guided from the adult experience. Methods: We conducted a retrospective single institution study of all children with HCM who had an ICD implanted from July 1999 through February 2016. Results: Thirty-three patients were identified. The mean age at ICD placement was 12.3±3 years with a mean follow up of 3.6±2.5 years. The mean maximal septal wall thickness Z score was 9.3± 2.9 and mean peak LV outflow tract gradient 17±12 mmHg. The median number of indications for ICD placement per patient was 3 (21%, 52%, 15% and 12% of the patients had 2, 3, 4 and 5 indications respectively). The most common indications were: severe HCM (Z-score ≥ + 6) (84%), abnormal blood pressure response to exercise (51%) and late gadolinium enhancement (LGE) (27%). Using the European Society of Cardiology HCM SCD risk calculator, the 5-year SCD risk was highest when the indication was ventricular tachycardia (VT). However, no patient with VT received ICD therapy (shock or anti tachycardia pacing (ATP)) during the study period. Fifteen patients received ICD therapy; 73% appropriately (73% a shock, 9% ATP and 18% both). Inappropriate shocks were delivered to 67% of the patients. One patient had slow rate VT (below the therapy zone) and one patient had ventricular fibrillation that did not elicit ICD therapy and required external defibrillation. The incidence rate ratios for appropriate ICD therapy were higher when the indication for the ICD placement was LGE (3.69), severe HCM (2.3) or compound heterozygosity (1.2) p &lt;0.05. The majority of patients (&gt;95%) were alive and free of transplant at 1 and 5 years after ICD placement. Conclusions: The risk stratification and selection of patients for ICD placement in the pediatric population is challenging. LGE, severe HCM and compound heterozygosity are associated with higher rate of appropriate ICD therapy. Optimal functioning of the ICD device in children and adolescents is difficult. The overall immediate survival and freedom from transplant is excellent.