tbuckley/cabot-search huggingface dataset:
Advanced epithelial ovarian cancer (EOC): Is there a place for maintenance therapy in patients with sub-optimal debulking?
Authors: R. Hariprasad, L. Kumar, S. Kumar, N. Bhatla, S. Thulkar, P. Das
Journal: Journal of Clinical Oncology (2009)

e14580 Background: Survival of patients with advanced epithelial ovarian cancer (EOC) with initial suboptimal debulking surgery (residual disease (&gt;1 cm) and those with recurrent EOC is poor. We used EGFR inhibitor gefitinib for maintenance and analyzed data on safety and toxicity. Methods: Between Nov. 2004 and Dec. 2008, Patients who achieved complete response (CR) following six cycles of paclitaxel and carboplatin received gefitinib as (Group I). Similarly, patients with recurrent EOC who achieved CR following six cycles of salvage CT received gefitinib (Group II). Both groups received gefitinib 250 mg once daily till evidence of relapse. Patients were examined every month and toxicity (CTC version II) was recorded. Serum CA-125 was done once in 2 months and CAT scan of abdomen &amp; pelvis every 6 month. The study was approved by Institute Ethics Committee and informed written consent was obtained from each patient. Results: A total of 48 patients (median age 47 years, range 23 to 63) have been recruited. Group I: 17 subjects and Group II 31 patients (1st relapse- 13, 2nd- 9, 3rd -6 &amp; 4th relapse in 3 patients). The mean duration of gefitinib treatment is 8.77 months (Gp-I: 14.4 months, Gp-II: 5.68 months). Toxicity was mainly in the form of skin rash &amp; diarrhea. Skin rash: 16 patients (33.3%); Group I - 8 (grade I-2, II-4, III-3,) &amp; Group II - 8 patients (grade I-3,II-4,III-1). Diarrhea: 12 patients (25%); Group I-3, group II- 9) all grade I. Two patients had both skin rashes and diarrhea. No pulmonary or hematological toxicity was observed. Currently, 13 patients are on gefitinib (mean duration of treatment 12.6 months); in 34 patients gefitinib has been discontinued due to relapse and in 1 patient due to grade III skin rashes over face. Among 18 patients with skin toxicity, 8 continue to be disease-free compared to 6 of 30 without skin toxicity (p=0.07). Conclusions: Gefitinib was tolerated well with mild toxicities limited to skin and GIT. Correlations between EGFR expressions vs. response may help to identify patients likely to benefit from gefitinib therapy. No significant financial relationships to disclose.
Quality of reports related to survival events in randomized clinical trials: A review of recent cancer trials published in eight major journals
Authors: S. Mathoulin-Pelissier, S. Gourgou-Bourgade, F. Bonnetain, A. Kramar
Journal: Journal of Clinical Oncology (2007)

6611 Background: About ten years ago, Altman pointed the low quality of survival analyses published in cancer journals. Despite the development of Consort statement, the lack of quality standards remained in the reports of randomized clinical trials (RCT).The aim of this study was to evaluate quality of definitions and reports of survival endpoints in recent cancer RCTs. Methods: A computerized search in Medline databases identified 274 cancer RCTs published from January 2004 to December 2004 in 4 general medical journals (BMJ, JAMA, Lancet, NEJM) and 4 clinical oncology journals (BJC, Cancer, JCO, JNCI). Eligible papers were these that reported primary analyses of RCT with survival endpoints. Three methodologists have reviewed and scored 1/3 of papers according to 7 key points: prevalence of adequate definition of survival end-points (time to origin, survival events, censures) and relevant information about their analyses (Kaplan-meier method, confidence interval, number of events, patients at risk). Reliability of scoring was checked among a random subsample of 30 papers with an independent biostatistician (kappa coefficient). Results: Following eligibility screening, 149 papers were not included. Among the 125 selected papers, 104 trials were of phase III (83%) and 98 publications (78%) were obtained from the 4 oncology journals. Among these RCTs, a total of 268 survivals endpoints were recorded and overall survival (OS) was the most frequent outcome (118 terms, 44%). Survival terms were adequately defined in 116 endpoints (43%) and OS was most frequent adequately defined (49%). Accurate information about analysis was found in 51 endpoints (19%). The less adequate information was patient's number at risk (55%). Finally, according to the 7 key methodological points, optimal quality of report was found in 19 of the endpoints (7 %) i.e.6 articles (kappa value: 0.65). Conclusions: Majority of published papers failed to provide an adequate definition and analysis reports of survival endpoints. Finally survival definitions add another source of variability actually not controlled. Readers should critically pay attention to the reported definitions since the lack of these elements may lead to misinterpretation of the RCT results. No significant financial relationships to disclose.
Yield of Lynch Syndrome Surveillance for Patients With Pathogenic Variants in DNA Mismatch Repair Genes
Authors: Anne Goverde, Ellis L. Eikenboom, Ellemieke L. Viskil, Marco J. Bruno, Michael Doukas, Winand N.M. Dinjens, Erik Jan Dubbink, Ans M.W. van den Ouweland, Robert M.W. Hofstra, Anja Wagner, Manon C.W. Spaander
Journal: Clinical Gastroenterology and Hepatology (2019)
Using plasma proteomic analysis for venous thromboembolism risk stratification in patients with advanced gastrointestinal cancers.
Authors: Haruka Itakura, Alison K Holzer, Lawrence V Hofmann, Philip S Tsao
Journal: Journal of Clinical Oncology (2012)

e21153 Background: Cancer patients represent 15-20% of the estimated 900,000 annual cases of venous thromboembolism (VTE) in the U.S., and thrombotic complications are the second most frequent cause of death in patients with cancer. Currently, no predictors or method exists by which patients with cancer can be accurately risk-stratified for thrombotic risk. Methods: Twenty-four patients with stage III/IV gastrointestinal (GI) cancers were followed for six months for incident VTE in a prospective cohort study. Twenty-nine biomarkers relevant to inflammation and thrombosis were tested for ability to discriminate between age- and sex- matched cancer patients with (n=10) and without incident VTE (n=14). Results: Expression levels of VCAM-1 and MMP-1 were statistically significantly elevated in VTE cases compared with controls in a series of univariate analyses. VCAM-1 remained statistically significant in a multivariate analysis. Conclusions: These findings suggest the role of VCAM-1 as a potential predictor of VTE in patients with GI cancers.
A New Classification of the Motor Anomalies of the Eye, based upon physiological principles, together with their symptoms, diagnosis and treatment.
Journal: JAMA (1897)

Our website uses cookies to enhance your experience. By continuing to use our site, or clicking "Continue," you are agreeing to our Cookie Policy | Continue JAMA HomeNew OnlineCurrent IssueFor Authors Publications JAMA JAMA Network Open JAMA Cardiology JAMA Dermatology JAMA Health Forum JAMA Internal Medicine JAMA Neurology JAMA Oncology JAMA Ophthalmology JAMA Otolaryngology–Head & Neck Surgery JAMA Pediatrics JAMA Psychiatry JAMA Surgery Archives of Neurology & Psychiatry (1919-1959) Podcasts Clinical Reviews Editors' Summary Medical News Author Interviews More JN Learning / CMESubscribeJobsInstitutions / LibrariansReprints & Permissions Terms of Use | Privacy Policy | Accessibility Statement 2023 American Medical Association. All Rights Reserved Search All JAMA JAMA Network Open JAMA Cardiology JAMA Dermatology JAMA Forum Archive JAMA Health Forum JAMA Internal Medicine JAMA Neurology JAMA Oncology JAMA Ophthalmology JAMA Otolaryngology–Head & Neck Surgery JAMA Pediatrics JAMA Psychiatry JAMA Surgery Archives of Neurology & Psychiatry Input Search Term Sign In Individual Sign In Sign inCreate an Account Access through your institution Sign In Purchase Options: Buy this article Rent this article Subscribe to the JAMA journal
P057 Artemether suppresses migration and invasion of fibroblast-like synoviocytes through inhibition of the rho signaling pathway in rheumatoid arthritis
Authors: J Jing, J-W Wang, Ma J-D, L-F Chen, L Dai
Journal: Annals of the Rheumatic Diseases (2019)

<h3>Career situation of first and presenting author</h3> Student for a master or a PhD. <h3>Introduction</h3> Experiments on collagen-induced arthritis rats showed that artemether, a new antimalarial drug derived from artemisinin, can reduce inflammatory cell infiltration, tissue edema, and bone erosion in the paws, which implied its potential efficacy in rheumatoid arthritis (RA). Fibroblast-like synoviocytes (FLS) in RA manifest tumor-like properties including increased adherence and invasiveness of adjacent cartilage and bone, resulting in joint destruction. However, effects of artemether on the aggressive properties of RA-FLS have not yet been elucidated. <h3>Objectives</h3> The aim of this study was to investigate the role and underlying mechanism of artemether on the migration and invasion of RA-FLS. <h3>Methods</h3> Synovial tissues were obtained by closed needle biopsy from 6 active RA patients and FLS were isolated and cultured <i>in vitro</i>. RA-FLS were treated with artemether at various concentrations, while methotrexate (MTX) and hydroxychloroquine (HCQ) were employed as controls. Cell viability, proliferation, cell-cycle, apoptosis, migration, invasion, and pseudopodium formation of RA-FLS were assessed by CCK-8 assays, EdU staining, Annexin V-FITC/PI staining, transwell assays, or F-actin staining respectively. The protein expression of RhoA, Rac1, and CDC42 were measured by Western blot. <h3>Results</h3> The IC<sub>50</sub> value of artemether, MTX and HCQ on RA-FLS were 988 µM, 181 nM and 5433 µM, respectively. Compared with untreated group, IC<sub>5</sub>-20μM of artemether, IC<sub>5</sub>-10nM of MTX and IC<sub>5</sub>-20μM of HCQ showed no effect on the proliferation, cell-cycle or apoptosis of RA-FLS. The transwell assays of migration and invasion showed that artemether (20 µM) significantly inhibited migration and invasion of RA-FLS and reduced lamellipodia and filopodia formations. Under the same IC<sub>5</sub> concentration, artemether (20 µM) showed similar inhibitory effects as MTX (10 nM), while HCQ (20 µM) showed no effect on migration and invasion of RA-FLS. Rho family proteins play important roles in modulating cell migration and invasion. Western blot analysis showed that artemether (20 µM) and MTX (10 nM) significantly reduced the expression of RhoA, Rac1, and CDC42 in RA-FLS, which indicated that artemether could inhibit the Rho signaling pathway. <h3>Conclusions</h3> Artemether can suppress the migration and invasion capability of RA-FLS through inhibiting the Rho signaling pathway. <h3>Acknowledgements</h3> This work was supported by National Natural Science Foundation of China (no. 81671612), Guangdong Natural Science Foundation (no. 2017A030313576, 2017A030310236) and Scientific Program of Traditional Chinese Medicine Bureau of Guangdong Province (no. 20161058, 20181058). <h3>Disclosure of Interest</h3> None declared.
Activity of hormonal treatment in uterine smooth muscle tumors of uncertain malignant potential (STUMP): A mono-institutional referral center experience in advanced disease.
Authors: Roberta Sanfilippo, Marta Sbaraglia, Elena Fumagalli, Giacomo Giulio Baldi, Giovanni Fucà, Carlo Morosi, Marta Barisella, Angelo Paolo Dei Tos, Paolo Giovanni Casali
Journal: Journal of Clinical Oncology (2019)

11066 Background: STUMP ecompass a group of uterine mesenchymal neoplasms in which the clinical behavior cannot be predicted on morphological grounds. A malignant clinical evolution is seen in approximately 10-20% of cases. When STUMP relapse, the label of “low-grade leiomyosarcoma” is sometimes found to be appropriate, though current histopathological criteria for uterine leiomyosarcoma (so called “Stanford criteria”) would exclude even the existence of low-grade uterine smooth muscle neoplasms. As they express ER and PR, hormonal treatment with GnRH inhibitors or aromatase inhibitors (AIs) may represent a therapeutic option. Methods: From October 2015, we have been treating with hormonal therapy relapsing patients with an initial diagnosis of STUMP, whose pathological aspect on retrospect was consistent with a “low-grade uterine leiomyosarcoma”. We identified 8 patients. Pathological diagnosis was centrally reviewed by expert sarcoma pathologists. Results: Eight pts were treated: 7 in first line; 1 pt in 4th line, following failure of chemotherapy (gemcitabine and taxotere, adriamycin and dacarbazine, trabectedin). Two premenopauseal pts were treated with GnRH inhibitors, 2 with a combination of GnRh inhibitors and an aromatase inhibitor, 3 with aromatase inhibitors only and 1 with selective progesterone-receptor modulator. 7 patients are evaluable for response and all of them had a partial response as best response. Median progression-free survival was 31 months. Conclusions: In our series, all patients with a centrally reviewed diagnosis retrospectively consistent with a “low grade uterine leiomyosarcoma” responded to hormonal treatment. Therefore, these pts may make up a subgroup with therapeutic and prognostic relevance. “Stanford criteria” need to be re-assessed, in an effort to improve prognostic and therapeutic stratification of uterine smooth muscle neoplasms, possibly shrinking the scope of currently defined STUMP.
Making Asthma Crystal Clear
Authors: John V. Fahy, Richard M. Locksley
Journal: New England Journal of Medicine (2019)

A recent study of Charcot–Leyden crystals, which are typically present in the airway mucus of persons with asthma and of persons with chronic rhinosinusitis with nasal polyps, indicates that they are immunogenic and that their dissolution — with the use of a nanobody — represents an experimental approach to treatment of allergic airway disease.
Recurrent 11q24.3 Gain Contributes to the Pathogenesis of Diffuse Large B Cell Lymphoma (DLBCL) by Deregulating ETS1 and FLI1
Authors: Paola Bonetti, Monica Testoni, Marta Scandurra, Maurilio Ponzoni, Roberto Piva, Afua Adjeiwaa Mensah, Maria Grazia Tibiletti, Ivo Kwee, Timothy C. Greiner, Wing C. Chan, Gianluca Gaidano, Miguel Piris, Emanuele Zucca, Francesco Bertoni
Journal: Blood (2011)
The Relation of Hospitals to Medical Education
Journal: New England Journal of Medicine (1967)

later.Dieulafoy and Bard 6 have each practised this method in pneumonía, with recovery in both cases.Others in France have also used it a few times, but I have not been able to get access to the journals in which the reports appeared.In three desperate cases in my service at the Massa- chusetts Hospital, this winter, I had turpentine in- jected, in one case on the ninth, in two on the seventh day of the disease.All three died, as seemed certain that they would, whatever was done or not done.I do not think that these cases should really count for, or against the method.For therapeutic purposes cases of pneumonia may be divided into three classes.First in frequency are those caseB which will recover under any treatment or no treatment, unless they are grossly mismanaged; second, those which will die in spite of any and all treatment known at present; third, those in which
Association of Change in N-Terminal Pro–B-Type Natriuretic Peptide Following Initiation of Sacubitril-Valsartan Treatment With Cardiac Structure and Function in Patients With Heart Failure With Reduced Ejection Fraction
Authors: James L. Januzzi, Margaret F. Prescott, Javed Butler, G. Michael Felker, Alan S. Maisel, Kevin McCague, Alexander Camacho, Ileana L. Piña, Ricardo A. Rocha, Amil M. Shah, Kristin M. Williamson, Scott D. Solomon
Journal: JAMA (2019)

In patients with heart failure and reduced ejection fraction (HFrEF), treatment with sacubitril-valsartan reduces N-terminal pro-b-type natriuretic peptide (NT-proBNP) concentrations. The effect of sacubitril-valsartan on cardiac remodeling is uncertain.To determine whether NT-proBNP changes in patients with HFrEF treated with sacubitril-valsartan correlate with changes in measures of cardiac volume and function.Prospective, 12-month, single-group, open-label study of patients with HFrEF enrolled in 78 outpatient sites in the United States. Sacubitril-valsartan was initiated and the dose adjusted. Enrollment commenced on October 25, 2016, and follow-up was completed on October 22, 2018.NT-proBNP concentrations among patients treated with sacubitril-valsartan.The primary outcome was the correlation between changes in log2-NT-proBNP concentrations and left ventricular (LV) EF, LV end-diastolic volume index (LVEDVI), LV end-systolic volume index (LVESVI), left atrial volume index (LAVI), and ratio of early transmitral Doppler velocity/early diastolic annular velocity (E/e') at 12 months.Among 794 patients (mean age, 65.1 years; 226 women [28.5%]; mean LVEF = 28.2%), 654 (82.4%) completed the study. The median NT-proBNP concentration at baseline was 816 pg/mL (interquartile range [IQR], 332-1822) and 455 pg/mL (IQR, 153-1090) at 12 months (difference, P < .001). At 12 months, the change in log2-NT-proBNP concentration was correlated with changes in LVEF (r = -0.381 [IQR, -0.448 to -0.310]; P < .001), LVEDVI (r = 0.320 [IQR, 0.246 to 0.391]; P < .001), LVESVI (r = 0.405 [IQR, 0.335 to 0.470]; P < .001), LAVI (r = 0.263 [IQR, 0.186 to 0.338]; P < .001), and E/e' (r = 0.269 [IQR, 0.182 to 0.353]; P < .001). At 12 months, LVEF increased from 28.2% to 37.8% (difference, 9.4% [95% CI, 8.8% to 9.9%]; P < .001), while LVEDVI decreased from 86.93 to 74.15 mL/m2 (difference, -12.25 mL/m2 [IQR, -12.92 to -11.58]; P < .001) and LVESVI decreased from 61.68 to 45.46 mL/m2 (difference, -15.29 mL/m2 [95% CI, -16.03 to -14.55]; P < .001). LAVI and E/e' ratio also decreased significantly. The most frequent adverse events were hypotension (17.6%), dizziness (16.8%), hyperkalemia (13.2%), and worsening kidney function (12.3%).In this exploratory study of patients with HFrEF treated with sacubitril-valsartan, reduction in NT-proBNP concentration was weakly yet significantly correlated with improvements in markers of cardiac volume and function at 12 months. The observed reverse cardiac remodeling may provide a mechanistic explanation for the effects of sacubitril-valsartan in patients with HFrEF.ClinicalTrials.gov Identifier: NCT02887183.
Prospective trial in early-stage breast cancer (EBC) patients (pts) submitted to nutrition evidence-based educational intervention: Early results of adherence to dietary guidelines (ADG) and body weight change (BWC).
Authors: Luisa Carbognin, Ilaria Trestini, Isabella Sperduti, Clelia Bonaiuto, Valentina Zambonin, Elena Fiorio, Daniela Tregnago, Veronica Parolin, Sara Pilotto, Giovanni Scambia, Giampaolo Tortora, Michele Milella, Emilio Bria
Journal: Journal of Clinical Oncology (2019)

11575 Background: Weight gain and overweight have been related to an increased risk of recurrence and mortality in patients affected by EBC. However, the adherence to nutritional intervention is not entirely explored. The aims of this prospective study were to evaluate the ADG and the effectiveness of nutritional intervention in terms of BWC in pts with EBC undergoing treatment. Methods: Entry criteria: EBC pts candidate to neoadjuvant/adjuvant therapy. At study entry, pts received a nutrition evidence-based tailored educational intervention by a skilled dietitian. Anthropometric and dietary assessments were performed. ADG was estimated through the validated Med-Diet 14-item questionnaire. Health-Related Quality of Life was analyzed with the EORTC QLQ-C30. Descriptive statistics was adopted. Associations between variables and groups according to nutritional variables were analysed (Chi-square test). Results: From February 2016 to December 2018, 204 pts were enrolled (median age 49 years): 27.5%/72.5% neoadjuvant/adjuvant treatment. At baseline, 2.5% of pts were underweight, 41.7% were normal weight, 33.3% were overweight and 22.5% were obese. Moreover, 47.5% of pts gained ≥5% of their usual weight and 25.5% performed physical activity. Significant nutritional impact symptoms were reported: dyspepsia (51.5%), constipation (62.3%) and dysgeusia (34.8%). The majority of pts presented dietary patterns high in fat (median fat intake: 35.2% from total energy intake) and low in dietary fiber (median dietary fiber intake: 17.2 g/day). A significant correlation between baseline BMI and tension was observed ( p &lt; 0.0001) as well as BMI and worry, irritability and depression ( p &lt; 0.0001, p &lt; 0.0001 and p = 0.008, respectively). Six months after the intervention, the median ADG was high (median Med-Diet score was 12). A high adherence to nutrition guidelines (defines as a Med-Diet score ≥10, 112 patients) significantly correlated with a weight loss ≥5% from the baseline weight ( p = 0.005). Furthermore, the weight loss ≥5% was correlated with a lower rate of depression ( p = 0.05). Conclusions: A tailored nutritional intervention for EBC pts undergoing adjuvant or neoadjuvant therapy has the potential to improve their ADG, in order to achieve a weight loss.
SGLT2 Inhibition with Empagliflozin Increases Circulating Provascular Progenitor Cells in People with Type 2 Diabetes Mellitus
Authors: David A. Hess, Daniella C. Terenzi, Justin Z. Trac, Adrian Quan, Tamique Mason, Mohammed Al-Omran, Deepak L. Bhatt, Natasha Dhingra, Ori D. Rotstein, Lawrence A. Leiter, Bernard Zinman, Sandra Sabongui, Andrew T. Yan, Hwee Teoh, C. David Mazer, Kim A. Connelly, Subodh Verma
Journal: Cell Metabolism (2019)
Adjuvant chemotherapy following curative intent hepatectomy for intrahepatic cholangiocarcinoma: Results from a multi-institutional analysis of 575 patients.
Authors: Dario Ribero, Antonio Daniele Pinna, Gennaro Nuzzo, Alfredo Guglielmi, Luca Aldrighetti, Stefano Maria Giulini, Giorgio Enrico Gerunda, Antonio Ponti, Mariano Tomatis, Francesco Leone, Massimo Aglietta, Pasquale Berloco, Fulvio Calise, Enrico Opocher, Salvatore Gruttadauria, Guido Torzilli, Lorenzo Capussotti
Journal: Journal of Clinical Oncology (2012)

4110 Background: Surgical resection alone is the standard of care for patients with resectable intrahepatic cholangiocarcinoma (IHC). This study evaluates the benefit of adjuvant chemotherapy ( Adj CTx) following curative intent hepatectomy for IHC. Methods: Clinicopathologic and long-term outcome data of 575 consecutive patients treated with curative intent hepatectomy for IHC (1995-2011) were extracted from a multi-institutional registry. After excluding operative mortality and M1 (n=46), Cox regression analysis was used to identify independent determinants of early recurrence (i.e., within 3 years). Propensity scores, which are used in observational studies to reduce selection bias by equating groups on the basis of relevant covariates, were calculated and utilized to match patients who had or had not Adj CTx (one-to-one match). Cases whose propensity score deviated more than 0.10 were considered unmatched and excluded from the analysis. Primary end-point was recurrence-free survival (RFS) at 3-years. Results: At a median FU of 42 months, 247 patients had recurred. Predictors of recurrence were LN metastases (HR 1.83 [1.36-2.44]), radical resection (HR 0.64 [0.45-0.9]), an elevated preoperative CA19.9 (HR 1.54 [1.15-2.07]), vascular invasion (HR 1.97 [1.49-2.61]), multiple tumors (HR 2.21 [1.71-2.86]), and size (analysed as continuous variable) (HR 1.01 [1.01-1.01]). After matching, no difference was observed between patients who had or had not Adj CTx (n=155 per group; 3-yrs RFS 28.3% vs. 38.0%, respectively; p=NS). When the analysis was restricted to patients who had gemcitabine, GEMOX or FOLFOX for 3 or more cycles (n=64 per group) again no difference emerged between patients who had or had not Adj CTx (3-yrs RFS 27.7% vs. 40.0% respectively, p=NS ). Conclusions: Our data suggest that Adj CTx following resection of IHC does not increase 3-years RFS.