tbuckley/cabot-search huggingface dataset:
Phase I and pharmacokinetic study of farletuzumab in solid tumors.
Authors: Yasutsuna Sasaki, Keisuke Miwa, Keishi Yamashita, Keiichi Fujiwara, Noriyuki Katsumata, Yasuhiro Fujiwara, Masayuki Namiki, Nozomu Koyanagi
Journal: Journal of Clinical Oncology (2012)

3084 Background: Farletuzumab (F) is a humanized monoclonal antibody against folate receptor α (FRA). Expression of FRA is reported to be 90% and 40% in ovarian cancer (OC) and gastric cancer (GC), respectively. The purpose of the study is to assess tolerability, pharmacokinetic profile and preliminary antitumor effect in solid tumors. Methods: Patients with OC or FRA expressing solid tumor who are resistant to standard treatments are eligible in the study. After pharmacokinetic (PK) run-in, F was administered by IV injection repeating every week until disease progression. PK profile was analyzed on day1 to day 10 in PK run-in and on day 22 to 29 in cycle 1. Dose limiting toxicities (DLTs) were defined as G4 hematological and G3/4 non-hematological toxicities by NCI-CTCAE. Dose escalation was planed in 4 cohorts (50, 100, 200 and 400mg/m 2 ). Results: Sixteen patients (14 OC and 2GC) received F infusion. Neither DLTs nor G3/4 toxicities were reported in all cohorts. As adverse events, G1/2 infusion reaction (44%), headache (44%), cytokine release syndrome (38%), nausea (31%) and appetite loss (31%) were observed and medically managed. AUC and C max. were increased dose-dependently and linear PK profiles were identified with median clearance between 6.02 and 10.54 mL/hr/m 2 in each cohort. No tumor shrinkage was recorded, but long-term disease stabilization for 22+ mos. and 10+ mos. were observed in one patient with clear cell OC (100mg/m 2 ) and one patient with GC (400 mg/m 2 ), respectively. No cumulative toxicities were observed in these 2 patients. Conclusions: The toxicities of F in Japanese patients were manageable with similar PK profile as compared with the US population (Konner et al. Clin Cancer Res 2010: 16; 5288-95). Long term disease stabilization is observed in subpopulation of clear cell OC and GC.
A SYSTEMATIC REVIEW AND META-ANALYSIS OF PROGNOSTIC SIGNIFICANCE OF ACQUIRED THROMBOCYTOPENIA AFTER PERCUTANEOUS CORONARY INTERVENTION ON IN-HOSPITAL AND 30-DAY CARDIOVASCULAR OUTCOMES IN CORONARY ARTERY DISEASE PATIENTS
Authors: Muhammad J. Ahsan, Hafiz Muhammad Fazeel, Noman Lateef, Saad Ullah Malik, Anosha Anwar, Syeda Hassan, Muryum Hassan, Azka Latif, Muhammad Qudrat Ullah, Aqsa Ashraf, Theresa Townley, Nancy Koster
Journal: Journal of the American College of Cardiology (2020)
LEFT VENTRICULAR CARDIAC MECHANICS IMPROVE IN PATIENTS POST TRANSCATHETER AORTIC VALVE REPLACEMENT REGARDLESS OF BASELINE LEFT VENTRICULAR FUNCTION
Authors: Stamatios Lerakis, Richard Ro, Karthik Seetharam, Prathyusha Bande, Kelash Kumar, Wenli Zhao, Parasuram Krishnamoorthy, Nagendra Boopathy Senguttuvan, George D. Dangas, Samin K. Sharma, Annapoorna Subhash Kini
Journal: Journal of the American College of Cardiology (2020)
THERAPEUTIC CONUNDRUM: PARADOXICAL SYSTEMIC, CEREBRAL AND PULMONARY EMBOLI WITH AN ACUTE BLEED
Authors: Jose Benjamin Cruz Rodriguez, Arjab Ghosh, Abbas Zaidi, Adriana Mares, Haider Alkhateeb, Harsha Nagarajarao, Chandra Prakash Ojha
Journal: Journal of the American College of Cardiology (2020)
Effect of nonmalignant accessory cells from the metastatic microenvironment on breast cancer cell resistance to antiestrogens.
Authors: Eugen Dhimolea, Constantine S. Mitsiades
Journal: Journal of Clinical Oncology (2013)

11039 Background: To address the role of the local metastatic microenvironment in the antiestrogen (AE) resistance exhibited by disseminated breast cancer (BrCa), we assembled heterotypic in vitro three-dimensional (3D) tissue cultures comprised of estrogen receptor-positive (ER+) BrCa cells and non-malignant accessory cells from organs frequently targeted by metastatic disease, to model the composition and architecture of metastatic lesions. Methods: MCF7 cells expressing luciferase, cultured alone or with accessory cells, were exposed to dose-ranges of hydroxytamoxifen (4-OHT), fulvestrant or raloxifene. MCF7 cells were also injected s.c. in nude mice either alone or with HS-5 bone marrow stromal cells (BMSCs). Tumor spheroid viability or xenograft growth were measured by bioluminescence. Results: MCF7 response to AEs in 3D conditions (collagen type I and/or Matrigel) was marked by acinar differentiation of tumor spheroids that resembles normal breast epithelium. Co-culture of MCF7 and immortalized accessory cells from the bone (BMSCs; HOBIT and hFOB osteoblasts), brain (SVGp12 astrocytes), liver (THLE3 hepatocytes), and lung (MRC9 fibroblasts) in 3D (but not 2D) conditions, conferred resistance to 4-OHT, raloxifene, and fulvestrant at clinically relevant doses. Heterotypic xenografts (MCF7 + BMSCs) had reduced response to tamoxifen compared with monotypic xenografts (MCF7 alone). BMSCs induced in MCF7 cells downregulation of TGFβ2; upregulation of a transcriptional signature enriched for genes associated with high-grade tumors, including genes involved in interferon response, signaling through EGFR superfamily members, NFkB and other antiapoptotic pathways; and elevated c-Myc protein levels. Exogenous TGFβ2 or neutralizing antibodies against INFγ partially re-sensitized MCF7 cells to 4-OHT in co-cultures. Conclusions: Our results indicate that accessory cells representing the microenvironment of metastatic sites confer AE resistance to BrCa cells in 3D tissue cultures and xenograft models. The mechanisms of stroma-induced AE resistance may reveal new therapeutic targets for refractory BrCa patients with metastatic disease.
ONE YEAR OUTCOMES FOLLOWING BIOPROSTHETIC VALVE FRACTURE TO FACILITATE VALVE-IN-VALVE TRANSCATHETER AORTIC VALVE REPLACEMENT
Authors: Adnan Chhatriwalla, Keith B. Allen, John Saxon, John Webb, Brian Whisenant, Steven J. Yakubov, James Harvey, Brian Matthew Stegman, Elaine Tseng, Marc Gerdisch, H. Edward Garrett, Carlos E. Sanchez, Paul Williams, Janarthanan Sathananthan, Hazem Alhawasli, Kevin Kennedy
Journal: Journal of the American College of Cardiology (2020)
Is Mitochondrial Dysfunction a Common Root of Noncommunicable Chronic Diseases?
Authors: Alexis Diaz-Vegas, Pablo Sanchez-Aguilera, James R Krycer, Pablo E Morales, Matías Monsalves-Alvarez, Mariana Cifuentes, Beverly A Rothermel, Sergio Lavandero
Journal: Endocrine Reviews (2020)

Abstract Mitochondrial damage is implicated as a major contributing factor for a number of noncommunicable chronic diseases such as cardiovascular diseases, cancer, obesity, and insulin resistance/type 2 diabetes. Here, we discuss the role of mitochondria in maintaining cellular and whole-organism homeostasis, the mechanisms that promote mitochondrial dysfunction, and the role of this phenomenon in noncommunicable chronic diseases. We also review the state of the art regarding the preclinical evidence associated with the regulation of mitochondrial function and the development of current mitochondria-targeted therapeutics to treat noncommunicable chronic diseases. Finally, we give an integrated vision of how mitochondrial damage is implicated in these metabolic diseases.
The impact of insurance health care on radiotherapy (RT) patterns of care in non-small cell lung cancer (NSCLC).
Authors: Brian E. Lally, Daniel M. Arsenault
Journal: Journal of Clinical Oncology (2012)

e16518 Background: Access to surgical care and imaging modalities in NSCLC patients are well documented to vary by race/ethnicity. Little information regarding disparities of RT technology usage in NSCLC patients exists. We studied the impact of insurance type on the utilization of radiation technology to investigate this further. Methods: We used the Florida Cancer Data System (FCDS) to create a cohort of adult, pathology-confirmed NSCLC patients who received external beam radiotherapy. Cases of NSCLC were included if they had complete information on date of diagnosis, type of insurance, and race (white or black; others were excluded). Only patients whose radiation therapy codes were either conformal radiotherapy (CRT) or intensity modulated radiotherapy (IMRT) were included. The chi square test was used to statistically assess the differences between the groups examined. Results: Our cohort included 2759 (92.7%) white patients and 218 (7.3%) black patients. 3.4% of white patients were uninsured vs 7.8% of black patients (p=0.007). Moreover, there was a statistically significant difference in the utilization of IMRT vs. CRT with respect to race (p=0.003). Specifically, 59.8% of white patients receive IMRT vs 49.5% of black patients. Subset analysis of white patients did not reveal a significant difference in RT technology utilization with respect to insurance status: 53.1% of uninsured white and 61.6% of insured white patients received IMRT (p=ns). However, a similar subset analysis of black patients revealed that only 17.6% of uninsured black patients and 48.5% of insured black patients received IMRT (p=0.045). Conclusions: The utilization of RT technology varied significant with respect to insurance status in the black population. An uninsured black patient is less likely to receive IMRT when compared to an uninsured white patient. Longer follow-up and clinical correlation is needed to determine the clinical significance of this finding, but work is needed rectify any potential disparities with respect to radiation therapy.
Randomized phase II trial of extended versus standard neoadjuvant therapy for esophageal cancer, NCCTG (Alliance) trial N0849.
Authors: Steven R. Alberts, Gamini S. Soori, Qian Shi, Dennis A. Wigle, Robert P. Sticca, Robert Clell Miller, James L. Leenstra, Patrick J. Peller, Tsung-Teh Wu, Harry H. Yoon, Timothy F. Drevyanko, Stephen Ko, Bassam Ibrahim Mattar, Daniel A. Nikcevich, Robert J. Behrens, Maged F. Khalil, George P. Kim
Journal: Journal of Clinical Oncology (2013)

4026 Background: Patients (pts) with locally advanced esophageal or gastroesophageal junction (GEJ) adenocarcinoma commonly receive neoadjuvant chemoradiotherapy (chemo-RT). Despite this approach the rate of recurrence remains high. Given the difficulties of postoperative therapy, the efficacy of extended neoadjuvant therapy was assessed. Methods: Eligibility criteria included T3-4,N0 – T any ,N(+) disease amenable to radiation and surgery. Pts were randomized to either arm A (docetaxel 60 mg/m 2 day 1 , oxaliplatin [Oxal] 85 mg/m 2 day 1, and capecitabine 1250 mg/m 2 /day days 1-14 x 2 cycles [DOC] followed by 5-FU 180 mg/m 2 /day continuous IV through radiation + Oxal 85 mg/m 2 days 1,15,29 + 50.4 Gy radiation (chemo-RT)) or arm B (chemo-RT alone). Randomization was stratified by ECOG PS (0/1 vs 2) and stage (II vs III/IVA). Primary endpoint was pathologic complete response (PCR) rate, defined as no gross or microscopic tumor identified in the surgical specimen. Interim analysis assessed efficacy and futility of the experimental intervention. Wilcoxon rank sum and Fisher’s exact tests were used to compare clinical/pathologic factors between arms. Results: Baseline and stratification factors were well balanced between arms. Of 42 pts included in the interim analysis (86% male; age [median 63, range 38-88], 100% PS 0/1; 71% stage III; 55% esophagus, 40% GEJ; 36% measurable disease), 4 and 1 pts in arms A and B, respectively, did not have surgery due to death (A, 2), progressive disease (A, 1), alternative treatment (A, 1) or adverse event (B, 1). Among 21 arm A pts, 21, 20, and 19 pts started 1 st cycle of DOC, 2 nd cycle of DOC and chemo-RT, respectively. All arm B pts received chemo-RT. 33% (7/21) of arm A and 48% (10/21) of arm B pts achieved PCR (p=0.53). Among pts undergoing surgery, 94% (16/17) and 100% (20/20) of arm A and B pts had complete resection (p=0.46). 38% and 24% of arm A and B pts experienced at least one grade 4+ adverse event at least possibly related to treatment (p=0.51). Conclusions: Extended neoadjuvant therapy in pts with locally advanced esophageal or GEJ adenocarcinoma failed to improve the PCR rate. Follow-up in regard to survival and rate of recurrence is ongoing. Clinical trial information: NCT00938470.
Epidermal growth factor receptor as a prognostic predictor to chemoradiotherapy in the primary lesion of esophageal squamous cell carcinoma.
Authors: Zhenhua Gao, Xue Meng, Dianbin Mu, Xindong Sun, Jinming Yu
Journal: Journal of Clinical Oncology (2013)

e15167 Background: Concurrent chemoradiotherapy (CCRT) is standard performed for patients with locally advanced esophageal squamous cell carcinoma (ESCC). Some reports have revealed that patients who responded well to CCRT had favorable outcomes, whereas poor responders conversely showed a worse prognosis. The aim of this study was to identify molecular markers predicting prognosis to CCRT. Methods: Forty-seven patients with locally advanced ESCC who were treated with CCRT were included in the present study.The regimen comprised 5-fluorouracil and cisplatinumcombined with radiation therapy (1.8-2Gy/day). The chemotherapy was repeated every 3 weeks and the total radical radiation dose was 60-64Gy.The clinicopathologic features, patterns of treatment failure, and survival data were compared with the expressions of epidermal growth factor receptor (EGFR), which were determined by immunohistochemistry in biopsy specimens obtained before treatment. Univariate and multivariate analyses were performed to determine the prognostic factors that influence patients survival. Results: Overall the indices of the overexprssions of EGFR (the percentage of immunoreactivetumor cells≥50%) in all patients were 59.6%. EGFR expression was no significantly associated with gender,age,tumor differentiation grade,tumor location,depth of invasion, and metastasis status except for lymph node status (P=0.011). A significant difference was seen in the overall survival between patients with or without EGFR overexpression group(P=0.024). However, overexpression of EGFR was not associated with local recurrence or distant metastasis.In addition, a relationship between overall survival and sex (P=0.021),age (P=0.018),T stage(P=0.035), and tumor location (P=0.023) was detected.Local recurrence was found has a relationship with T stage(P=0.015) and metastasis status (P=0.026),and distant metastasis was found has a relationship with age (P=0.048). Conclusions: EGFR overexpression determined in pretreatment biopsy specimens maybe a clinically useful biomarker for predicting the overall survival of ESCC patients.
LATE GADOLINIUM ENHANCEMENT MRI AS A NOVEL SCREENING MODALITY FOR ESOPHAGEAL THERMAL INJURY AFTER ATRIAL FIBRILLATION ABLATION
Authors: Qussay Marashly, Chaitra Gopinath, Alex Baher, Madan M. Acharya, Mossab Aljuaid, Mobin Kheirkhahan, Nassir F. Marrouche, Mihail Chelu
Journal: Journal of the American College of Cardiology (2020)
PERFORMANCE OF NOVEL BIOMARKER-CLINICAL SCORE TO PREDICT PRESENCE OF OBSTRUCTIVE CORONARY DISEASE VERSUS STRESS TEST IN VALIDATION COHORT
Authors: Emmanuel Ekanem, Palak Shah, Federica Latta, Grady Barnes, Elizabeth Adams, Craig Magaret, Celine Peters, Rhyne Rhonda, Christopher R. DeFilippi
Journal: Journal of the American College of Cardiology (2020)
When Guidelines Recommend Shared Decision-making
Authors: Doreen M. Rabi, Marleen Kunneman, Victor M. Montori
Journal: JAMA (2020)

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
INCIDENCE AND CLINICAL PREDICTORS OF ADVERSE EVENTS IN ADULTS AFTER TOTAL CAVOPULMONARY FONTAN PALLIATION
Authors: Christopher Anigwe, Vidhushei Yogeswaran, Anita Moon-Grady, Anika Aggarwal, Sarah Blissett, Ian Stewart Harris, Peter Kouretas, Vaikom S. Mahadevan, Elyse Foster, Anushree Agarwal
Journal: Journal of the American College of Cardiology (2020)
Risk of neuroinflammatory events in arthritis patients treated with tumour necrosis factor alpha inhibitors: a collaborative population-based cohort study from Denmark and Sweden
Authors: Tine Iskov Kopp, Bénédicte Delcoigne, Elizabeth V Arkema, Rikke Kart Jacobsen, Melinda Magyari, Else Helene Ibfelt, Henning Locht, Finn Sellebjerg, Rene Lindholm Cordtz, Dorte V Jensen, Johan Askling, Lene Dreyer
Journal: Annals of the Rheumatic Diseases (2020)

Objectives To investigate whether tumour necrosis factor alpha inhibitors (TNFis) are associated with an increased risk of neuroinflammatory diseases among patients with arthritic diseases. Methods Cohorts of patients with rheumatoid arthritis (RA, n=25 796), psoriatic arthritis (PsA, n=8586) and ankylosing spondylitis (AS, n=9527) who initiated a TNFi treatment year 2000–2017 were identified from nationwide clinical rheumatology registers in Sweden and Denmark. Information on demyelinating disease and inflammatory neuropathy diagnoses was retrieved from prospective linkage to National Patients Register. A Cox proportional hazard model was used to estimate HRs and 95% CI comparing TNFi exposed and non-exposed, by disease and country. Results Among 111 455 patients with RA, we identified 270 (Sweden) and 51 (Denmark) events (all types of neuroinflammatory diseases combined), corresponding to crude incidence rates (per 1000 person-years) of 0.37 (Sweden) and 0.39 (Denmark) in TNFi-treated patients vs 0.39 (Sweden) and 0.28 (Denmark) in unexposed patients, and an age-sex-calendar-period-adjusted HR (95% CI) of 0.97 (0.72 to 1.33) (Sweden) and 1.45 (0.74 to 2.81) (Denmark) in TNFi exposed compared with non-exposed patients. For a total of 64 065 AS/PsA patients, the corresponding numbers were: 196 and 32 events, crude incidence rates of 0.59 and 0.87 in TNFi-treated patients vs 0.40 and 0.19 in unexposed patients, and HRs of 1.50 (1.07 to 2.11) and 3.41 (1.30 to 8.96), for Sweden and Denmark, respectively. For multiple sclerosis, the patterns of HRs were similar. Conclusions Use of TNFi in AS/PsA, but not in RA, was associated with increased risk of incident neuroinflammatory disease, though the absolute risk was below one in 1000 patients/year.
Monitoring Crimean-Congo haemorrhagic fever virus RNA shedding in body secretions and serological status in hospitalised patients, Turkey, 2015
Authors: Dilek Yagci-Caglayik, Bircan Kayaaslan, Derya Yapar, Aysel Kocagul-Celikbas, Aslinur Ozkaya-Parlakay, Mestan Emek, Nurcan Baykam, Hasan Tezer, Gulay Korukluoglu, Aykut Ozkul
Journal: Eurosurveillance (2020)

IntroductionCrimean-Congo haemorrhagic fever (CCHF) is a tick-borne disease in Africa, Asia, the Balkan peninsula, the south-east of Europe and the Middle East, with mortality rates of 3-30%. Transmission can also occur through contact with infected animals or humans.AimThis observational, prospective case series aimed to investigate detectable viral genomic RNA in whole-body fluids and antibody dynamics in consecutive daily samples of patients diagnosed with CCHF until discharge from hospital.MethodsWe tested 18 patients and 824 swabs and sera with RT-PCR and 125 serum samples serologically.ResultsThe longest duration until clearance of viral RNA was 18 days from serum collection and 18, 15, 13, 19 and 17 days, respectively, from nasal, oral, genital (urethral or vaginal) and faecal swab, and urine. In seven patients, viral load decreased in serum at the same time as it increased in urine or persisted at the same logarithmic values. Despite clearance in serum, viral RNA was detected in faeces and genital swabs in two and three patients, respectively. Viral clearance from body fluids occurred earlier than from serum in eight patients on ribavirin treatment. The shortest seroconversion time was 3 days after symptom onset for IgM and IgG. Seroconversion of IgG occurred until Day 14 of symptoms.ConclusionWe report persistence of viral RNA in urine, faeces and genital swabs despite serum clearance. This may indicate a need for extending isolation precautions, re-evaluating discharge criteria and transmission risk after discharge, and considering oral swabs as a less invasive diagnostic alternative.
Mortality from other malignancies in bladder cancer survivors.
Authors: Hamed Ahmadi, Eila C. Skinner, Gus Miranda, Jie Cai, Hooman Djaladat, Scott Leslie, Siamak Daneshmand
Journal: Journal of Clinical Oncology (2012)

4589 Background: Other-cause mortality represents a considerable proportion of overall long-term mortality in bladder cancer (BC) patients who underwent curative radical cystectomy (RC). Other malignancies besides BC are reportedly among the most common etiologies of other-cause mortality. We report on mortality from other malignancies in BC survivors who have undergone prior RC. Methods: Data on BC patients who died of other malignancies were derived from a cohort of 1964 patients with pathologic diagnosis of urothelial carcinoma of bladder who underwent RC with intent to cure due to BC at University of Southern California between 1971 and 2008. For subsequently developed malignancies, the time interval between RC and occurrence of malignancy was calculated. Other malignancies mortality was evaluated with respect to gender, pathological stage of BC, and type of malignancy. Results: Other malignancies were diagnosed in 463 (23.5%) patients. They were the cause of death in 122 (6.21%) patients (109 male) who had a median age of 68.6 (range 43.4 – 88.7) at time of RC. Of all 122 patients with other malignancies, 22(18%) patients were diagnosed prior to RC, 5 (4%) concurrently with BC diagnosis, and 94 (77%) subsequent to RC. At the time of cystectomy, 87/122 (71.3%) patients had lymph node-negative organ-confined disease, compared to 56.3% in the whole cohort; and 18 (14.7%) patients had nodal disease, compared to 23.2% in the whole cohort. 116/122 (95%) of these patients had no evidence of BC recurrence at time of death. Secondary cancers occurred at a median of 7.7 years (Range 3 months – 29.9 years) after RC. Most common sites and types of malignancies that led to death were lung in 43/122 (35.2%), predominantly non-small cell carcinoma in 17/43(39.5%); hematologic in 15/122 (12.3%), largely lymphoma in 6/15 (40%); and colon in 11/122 (9%), primarily adenocarcinoma in 8/11 (72.7%) patients. Conclusions: Lung, hematologic, and colon cancers are the most common causes of death due to other malignancies in BC survivors and more commonly found in male patients with lymph node-negative organ-confined tumor. Continued screening for other cancers in the follow-up of BC survivors may be warranted.