tbuckley/cabot-search huggingface dataset:
Replication of associations between genetic polymorphisms and chronic graft-versus-host disease
Authors: Paul J. Martin, Wenhong Fan, Barry E. Storer, David M. Levine, Lue Ping Zhao, Edus H. Warren, Mary E. D. Flowers, Stephanie J. Lee, Paul A. Carpenter, Michael Boeckh, Sangeeta Hingorani, Li Yan, Qiang Hu, Leah Preus, Song Liu, Stephen Spellman, Xiaochun Zhu, Marcelo Pasquini, Philip McCarthy, Daniel Stram, Xin Sheng, Loreall Pooler, Christopher A. Haiman, Lara Sucheston-Campbell, Theresa Hahn, John A. Hansen
Journal: Blood (2016)
Adjuvant chemotherapy (ACT) in stage III colon cancer: A study of 156,240 patients from 1985–2001
Authors: J. M. Jessup, F. Greene, B. Minsky, A. Stewart
Journal: Journal of Clinical Oncology (2004)

3533 Background: A 1990 NIH Consensus Conference recommended that Stage III colon cancer patients receive ACT based on improved survival in randomized trials. Our purpose was to determine whether ACT is standard of practice in the community and if it has improved survival. The National Cancer Data Base (NCDB), a project of the Commission on Cancer (American College of Surgeons), was used to assess patterns of care and outcomes. Methods: Data from 156,240 stage III colon cancer patients treated in 1902 hospitals were entered prospectively between 1985 and 2001 and included standard clinical, demographic and treatment variables. Standard statistical analysis was performed to assess associations between these variables and 5 year relative survival. Results: 1) demographics were stable over time with 52.6% women, 22% 80+ years old, and 23.8% minorities; 2) differentiation (27.5% high grade) and T stage (88.2%) were stable but N2 Nodes increased - 28.3% (1991) to 31.3% (2001, P<0.0001); 3) ACT use increased from 9.5% (1985) to 52.2% (1991) to 63% (2001); 4) ACT use was similar by ethnicity but 4% more women only received surgery; 5) ACT use was similar by grade, T and N stage; 6) ACT use increased in older patients by 15 - 19% in 70–79 and 80+ (1990 to 2001) but is given to <40% of 80+; 6) Survival for Stage III colon cancer treated by surgery alone was 48.7 - 53.4% for patients treated 1991 -1996 but ACT use improved survival by 10% (1991) that increased to 16.7% (1996) over surgery alone. Conclusions: ACT use has increased, is standard of practice and has increased survival of Stage III colon cancer patients. However, more women and older patients should receive ACT if community survival in Stage III colon cancer is to improve further. No significant financial relationships to disclose.
Multiple primary neoplasms involving the breast
Authors: L. S. Maddali, S. Maddali
Journal: Journal of Clinical Oncology (2006)

10786 Background: Multiple Primary Neoplasms (MPN) are being identified with increasing frequency in Breast cancer patients. We studied MPN involving Breast cancer as at least one primary for (1) incidence and (2) identifying. subsets with special features. Methods: 83 patients with MPN were identified among 3378 patients seen between January 1 st 1999 and 31st December 2005. (2.15%). 40 of these had Breast primary (48.19%). which form the basis of the present report. One or both primaries were identified during this period. But in some cases with primaries in remote past, available documentation was accepted. Results: Breast cancer was the Index cancer 31/40 (77.50%)and second primary in 9/40 (22.50%). Among the index cancers, 4/31 cases (12.90%) were synchronous and 27/31 (87.10%) were metachronous. 100% of the second primary in breast group were metachronous. Breast-Breast MPN 15/40 (37.50%) and Breast-Non breast MPN 25/40 (62.50%). Mean ages for Breast-Breast MPN 47.33 years, Synchronous tumors 38.66 yrs, metachronous tumors 58.20 yrs, Breast-Non Breast MPN 55.44 yrs. Mortality for Breast-Breast MPN as a group was 73.33%, synchronous tumors (2/3) 66.67%, metachronous tumors (10/12) 83.33%, Breast-Non Breast MPN, metachronous tumors (13/24) 54.17%. When the interval between index and second primary was studied, the Breast-Breast MPN mortality was (7/9) 77.78% for 2 yrs or less duration, (3/3) 100% for more than 2yrs. For Breast-NonBreast MPN, mortality was (6/9) 66.67% for duration of 2 yrs or less and (7/15) 46.67% for more than 2 yrs. The common malignancies associated in the index Breast cancer group were from Ovary (6),Thyroid (2),pancreas (2), Hematologic neoplasms (3) Upper Aero Digestive Tract (2). The second primary Breast cancer group had primaries in ovary (2), colon (2), hematologic (3) neoplasms. Conclusions: Breast-Breast MPN are seen in younger patients with higher mortality than Breast-Non Breast MPN. In the Breast-Non Breast MPN group, longer interval between the primaries is associated with lower mortality. There were no major differences between the Index Breast cancer group and Breast Second Primary group. Mortality appeared to be determined by the nature of the Non Breast Primary. No significant financial relationships to disclose.
Mammalian target of rapamycin inhibition counterbalances the inflammatory status of immune cells in patients with chronic granulomatous disease
Authors: Aurélie Gabrion, Isabelle Hmitou, Despina Moshous, Bénédicte Neven, Alain Lefèvre-Utile, Jean-Sébastien Diana, Félipe Suarez, Capucine Picard, Stéphane Blanche, Alain Fischer, Marina Cavazzana, Fabien Touzot
Journal: Journal of Allergy and Clinical Immunology (2016)
CD8+ T Cells Contribute to the Development of Coronary Arteritis in the <i>Lactobacillus casei</i> Cell Wall Extract–Induced Murine Model of Kawasaki Disease
Authors: Magali Noval Rivas, Youngho Lee, Daiko Wakita, Norika Chiba, Jargalsaikhan Dagvadorj, Kenichi Shimada, Shuang Chen, Michael C. Fishbein, Thomas J. A. Lehman, Timothy R. Crother, Moshe Arditi
Journal: Arthritis & Rheumatology (2016)

Objective Kawasaki disease (KD) is the leading cause of acquired heart disease among children in developed countries. Coronary lesions in KD in humans are characterized by an increased presence of infiltrating CD3+ T cells; however, the specific contributions of the different T cell subpopulations in coronary arteritis development remain unknown. Therefore, we sought to investigate the function of CD4+ and CD8+ T cells, Treg cells, and natural killer (NK) T cells in the pathogenesis of KD. Methods We addressed the function of T cell subsets in KD development by using a well‐established murine model of Lactobacillus casei cell wall extract (LCWE)–induced KD vasculitis. We determined which T cell subsets were required for development of KD vasculitis by using several knockout murine strains and depleting monoclonal antibodies. Results LCWE‐injected mice developed coronary lesions characterized by the presence of inflammatory cell infiltrates. Frequently, this chronic inflammation resulted in complete occlusion of the coronary arteries due to luminal myofibroblast proliferation (LMP) as well as the development of coronary arteritis and aortitis. We found that CD8+ T cells, but not CD4+ T cells, NK T cells, or Treg cells, were required for development of KD vasculitis. Conclusion The LCWE‐induced murine model of KD vasculitis mimics many histologic features of the disease in humans, such as the presence of CD8+ T cells and LMP in coronary artery lesions as well as epicardial coronary arteritis. Moreover, CD8+ T cells functionally contribute to the development of KD vasculitis in this murine model. Therapeutic strategies targeting infiltrating CD8+ T cells might be useful in the management of KD in humans.
Long-term outcome of 6-month maintenance chemotherapy for acute lymphoblastic leukemia in children
Authors: M Kato, S Ishimaru, M Seki, K Yoshida, Y Shiraishi, K Chiba, N Kakiuchi, Y Sato, H Ueno, H Tanaka, T Inukai, D Tomizawa, D Hasegawa, T Osumi, Y Arakawa, T Aoki, M Okuya, K Kaizu, K Kato, Y Taneyama, H Goto, T Taki, M Takagi, M Sanada, K Koh, J Takita, S Miyano, S Ogawa, A Ohara, M Tsuchida, A Manabe
Journal: Leukemia (2016)
Factors of interindividual hematopoietic toxicity of carboplatin.
Authors: E. Chatelut, A. Schmitt, N. Penel, M. Campone, R. Largillier, P. Soulié, M. Fabbro, N. Houede, J. Medioni, P. Bougnoux
Journal: Journal of Clinical Oncology (2010)

2568 Background: AUC dosing is routinely carried out for carboplatin but the chosen target AUC values are largely empirical. This multicenter pharmacokinetic-pharmacodynamic study was performed to determine the pharmacodynamic covariates involved in the interindividual variability of carboplatin hematotoxicity. Methods: The 383 patients included in the study were receiving carboplatin as part of established protocols. A semi-physiological population pharmacokinetic-pharmacodynamic model using the program NONMEM was applied to describe the time-course of neutrophil and platelet counts. The plasma ultrafiltrable carboplatin concentration (Conc) was assumed to inhibit the proliferation of blood cell precursors through a linear model: Drug effect = Slope × Conc. The slope corresponds to the patients' sensitivity to carboplatin hematotoxicity. The relationships between the patients' sensitivity to neutropenic or thrombopenic effects of carboplatin and eighteen demographic, biological and pharmacogenetic covariates were studied. The database was split into a construction (276 patients) and a validation database (107 patients). Results: The thrombocytopenic effect of carboplatin showed a high interindividual variability. The slope value was decreased by 33% in case of concomitant paclitaxel chemotherapy. Previous chemotherapy was associated with a lower (−21%) basal platelet count. For the neutropenic effect, the slope value was increased by 86% when carboplatin was combined with other cytotoxics in comparison with monochemotherapy. An external validation of the model was done by both re-estimation of the parameters and a visual predictive check based on the validation dataset. Conclusions: This analysis enabled a prediction to be made of the percentage of patients presenting a risk of major hematotoxicity, depending on the AUC for the different subgroups of patients, defined according to significant pharmacodynamic covariates. No significant financial relationships to disclose.
IgE-associated allergic disorders: recent advances in etiology, diagnosis, and treatment
Authors: F. Zellweger, A. Eggel
Journal: Allergy (2016)

Abstract IgE‐associated allergic diseases belong to the most common inflammatory conditions. Their clinical manifestation ranges from mild symptoms to life‐threatening episodes. Often patients experience a reduction in physical and psychologic well‐being and suffer from a decreased quality of life due to disease activity. The continuously rising number of people that are affected by an allergic condition indicates an urgent need for better diagnostics and more efficient treatment options. Recent progress in the understanding of pathophysiologic mechanisms underlying IgE‐associated allergic disorders has led to the identification of novel therapeutic targets and the development of drug candidates that are currently under evaluation. In this review, we highlight studies and clinical trials, which have helped to gain further insight in the etiology of IgE‐associated allergic conditions as well as advances in the development of diagnostic tools and therapeutic approaches recently published in Allergy (European Journal of Allergy and Clinical Immunology) .
Mucosal bridge formation in a patient with esophageal epidermoid metaplasia
Authors: Elena Salamun, Hans Gröchenig, Cord Langner
Journal: Endoscopy (2016)

Esophageal mucosal bridge formation is an uncommon condition that is believed to result from mucosa injury. Ingestion of corrosive agents, mediastinal radiation therapy, and variceal sclerotherapy have been identified as possible causes, but mucosal bridges within the esophagus have also been described in chronic inflammatory conditions such as Crohn's disease [1] [2].
Phase II study of XL184 (BMS 907351), an inhibitor of MET, VEGFR2, and RET, in patients (pts) with progressive glioblastoma (GB).
Authors: P. Y. Wen, M. Prados, D. Schiff, D. A. Reardon, T. Cloughesy, T. Mikkelsen, T. Batchelor, J. Drappatz, M. C. Chamberlain, J. F. De Groot
Journal: Journal of Clinical Oncology (2010)

2006 Background: XL184 is an oral, potent inhibitor of MET, VEGFR2 and RET that has demonstrated clinical antitumor activity. In solid tumors, the MTD was 175 mg qd. Elevated levels of VEGFR2 and MET are found in GB, the latter correlated with poor prognosis. Methods: XL184 was studied in two cohorts of previously treated GB pts at 175 and 125 mg qd. The 125 mg cohort was added to further optimize tolerability while maintaining activity. Pts with and without prior antiangiogenic therapy (AAT) were allowed. Primary objectives include independent centrally confirmed (IRF) overall response rate (ORR), 6-month progression-free survival (PFS6) and safety. Secondary objectives include duration of response, survival, and changes in steroid usage. Plasma biomarkers were assessed for evidence of target inhibition. Results: Interim results are presented for 124 pts enrolled with a median age 55 yrs (range: 21-73); 42 (34%) had prior AAT, 42 (34%) were in second relapse, and 48 (39%) required corticosteroids at baseline. In the 175 mg qd cohort (n = 46) PFS6 (all pts) was 21%; ORR in AAT-naïve (n = 34) and AAT-pretreated pts (n = 12) was 21% and 8%, respectively; median duration of response was 5.9 months (range: 1.9-12.8). In the 125 mg qd cohort, ORR in response- evaluable AAT-naïve (n = 25) pts was 32%, with a median duration of response not yet reached. The rate of ≥ 50% decline in size of enhancing lesions at ≥ 1 timepoint, in response-evaluable AAT-naïve pts for the 175 mg and 125 mg qd cohorts was 41% and 60%, respectively. Decrease in size of enhancing lesions has been observed in some AAT-pretreated pts. Most frequent Gr3/4 AEs were fatigue (23%), hypophosphatemia (10%), serum lipase elevation (10%) and ALT, headache, lymphopenia and convulsion (9% each). Dose interruption/reduction, AEs related to TKI/VEGFR-inhibition (hypertension, proteinuria, bleeding, hand-foot syndrome), and modulation of plasma biomarkers for VEGFR and MET inhibition (VEGF-A, PlGF, sVEGFR2, sMET) were observed at both doses. Conclusions: XL184 demonstrates clinical activity and target inhibition of MET and VEGFR2 at 175 mg and 125 mg qd in pts with progressive GB, including pts with prior AAT. Longer follow-up will allow better risk/benefit evaluation. Author Disclosure Employment or Leadership Position Consultant or Advisory Role Stock Ownership Honoraria Research Funding Expert Testimony Other Remuneration Exelixis Exelixis Exelixis
I Had to Get Cancer to Become a More Empathetic Doctor
Authors: Carl Norden
Journal: Annals of Internal Medicine (2016)

On Being a Patient4 October 2016I Had to Get Cancer to Become a More Empathetic DoctorCarl Norden, MDCarl Norden, MDFrom Drexel School of Medicine, Philadelphia, Pennsylvania.Author, Article, and Disclosure Informationhttps://doi.org/10.7326/M16-1243 Audio Reading - "I Had to Get Cancer to Become a More Empathetic Doctor" Audio. Michael A. LaCombe, MD, Annals Associate Editor, reads "I Had to Get Cancer to Become a More Empathetic Doctor," by C. Norden. Your browser does not support the audio element. Audio player progress bar Step backward in current audio track Play current audio trackPause current audio track Step forward in current audio track Mute current audio trackUnmute current audio track 00:00/ SectionsAboutFull TextPDF ToolsAdd to favoritesDownload CitationsTrack CitationsPermissions ShareFacebookTwitterLinkedInRedditEmail Listen to the patient—they are telling you the diagnosis. I first heard these words, apocryphally attributed to Sir William Osler, from the white-haired senior physician at Harvard who greeted us on our first day of medical school in 1956. For the last 50-plus years, I have taught this as a guiding precept to medical students and residents. "Listen, you learn from what patients tell you, both spoken and unspoken." I still teach that to the fellows at Temple Medical School and the medical students at Drexel. I am 80 and a retired infectious diseases physician. I've always thought of myself ... Author, Article, and Disclosure InformationAffiliations: From Drexel School of Medicine, Philadelphia, Pennsylvania.Corresponding Author: Carl Norden, MD, Drexel School of Medicine, 440 South Broad Street, Philadelphia, PA 19146; e-mail, [email protected]com. PreviousarticleNextarticle Advertisement Audio Reading - "I Had to Get Cancer to Become a More Empathetic Doctor" Audio. Michael A. LaCombe, MD, Annals Associate Editor, reads "I Had to Get Cancer to Become a More Empathetic Doctor," by C. Norden. Your browser does not support the audio element. Audio player progress bar Step backward in current audio track Play current audio trackPause current audio track Step forward in current audio track Mute current audio trackUnmute current audio track 00:00/ FiguresReferencesRelatedDetails Metrics Cited byEthics and the Legalization of Physician-Assisted Suicide: An American College of Physicians Position PaperLois Snyder Sulmasy, JD and Paul S. Mueller, MD, MPH, for the Ethics, Professionalism and Human Rights Committee of the American College of Physicians*Pazopanib 4 October 2016Volume 165, Issue 7Page: 525-526KeywordsAdrenal glandsAnxietyEmotionsFearInfectious diseasesKidneysRed blood cellsTasteUltrasound imagingVomiting ePublished: 4 October 2016 Issue Published: 4 October 2016 Copyright & PermissionsCopyright © 2016 by American College of Physicians. All Rights Reserved.PDF downloadLoading ...
Effect of topical imiquimod as primary treatment for lentigo maligna: the LIMIT-1 study
Authors: J.R. Marsden, R. Fox, N.M. Boota, M. Cook, K. Wheatley, L.J. Billingham, N.M. Steven
Journal: British Journal of Dermatology (2016)

Topical imiquimod is sometimes used for lentigo maligna (LM) in situ melanoma instead of surgery, but frequency of cure is uncertain. Pathological complete regression (pCR) is a logical surrogate marker for cure after imiquimod, although residual LM and atypical melanocytic hyperplasia may not be reliably distinguished. A trial comparing imiquimod vs. surgery might be justified by a high imiquimod pCR rate. Primary: to estimate the pCR rate for LM following imiquimod. Secondary: to assess the accuracy of prediction of pCR, using clinical complete regression (cCR) plus negative post‐treatment biopsies, tolerability, resource use, patients' preferences and induced melanoma immunity. This was a single‐arm phase II trial of 60 imiquimod applications over 12 weeks for LM then radical resection. A pCR rate ≥ 25 out of 33 would reliably discriminate between pCR rates < 60% and ≥ 85%. Clinical response was assessed and biopsies taken after imiquimod. Patients recorded adverse events in diaries. Patient preference was measured after surgery using a standard gamble tool. The pCR rate was 10 of 27 (37%, 95% confidence interval 19–58%). The rate of cCR plus negative biopsies was 12 of 28, of whom seven of 11 had pCR on subsequent surgery. The median dose intensity was 86·7%. Of the 16 surveyed patients, eight preferred primary imiquimod over surgery if the cure rate for imiquimod was 80%, and four of 16 if it was ≤ 40%. The pCR rate was insufficient to justify phase III investigation of imiquimod vs. surgery. Clinical complete response and negative targeted biopsies left uncertainty regarding pathological clearance. Some patients would trade less aggressive treatment of LM against efficacy.
Outcome of Relapse after Reduced-Intensity Allogeneic Hematopoietic Stem Cell Transplantation (HSCT) - The Effect of the Underlying Disease on Survival Following Relapse.
Authors: Seema Singhal, Olga Frankfurt, Andrew Evens, Leo Gordon, Martin Tallman, Stephanie Williams, Jane Winter, David Grinblatt, Lynne Kaminer, Jayesh Mehta
Journal: Blood (2007)
Birefringence microscopy platform for assessing airway smooth muscle structure and function in vivo
Authors: David C. Adams, Lida P. Hariri, Alyssa J. Miller, Yan Wang, Josalyn L. Cho, Martin Villiger, Jasmin A. Holz, Margit V. Szabari, Daniel L. Hamilos, R. Scott Harris, Jason W. Griffith, Brett E. Bouma, Andrew D. Luster, Benjamin D. Medoff, Melissa J. Suter
Journal: Science Translational Medicine (2016)

The inability to visualize airway smooth muscle (ASM) cells in vivo is a major obstacle in understanding their role in normal physiology and diseases. At present, there is no imaging modality available to assess ASM in vivo. Confocal endomicroscopy lacks the penetration depth and field of view, and conventional optical coherence tomography (OCT) does not have sufficient contrast to differentiate ASM from surrounding tissues. We have developed a birefringence microscopy platform that leverages the micro-organization of tissue to add further dimension to traditional OCT. We have used this technology to validate ASM measurements in ex vivo swine and canine studies, visualize and characterize volumetric representations of ASM in vivo, and quantify and predict ASM contractile force as a function of optical retardation. We provide in vivo images and volumetric assessments of ASM in living humans and document structural disease variations in subjects with mild asthma. The opportunity to link inflammatory responses to ASM responses and to link ASM responses to clinical responses and outcomes could lead to an increased understanding of diseases of the airway and, ultimately, to improved patient outcomes.
The Future of Cardiac Imaging
Authors: Pamela S. Douglas, Manuel D. Cerqueira, Daniel S. Berman, Kavitha Chinnaiyan, Meryl S. Cohen, Justin B. Lundbye, Rajan A.G. Patel, Partho P. Sengupta, Prem Soman, Neil J. Weissman, Timothy C. Wong, Federico Asch, Timothy M. Bateman, Daniel S. Berman, Ginger Biesbrock, Jeffrey Brinker, David Brophy, Manuel Cerqueira, Kavitha Chinnaiyan, Meryl Cohen, Vasken Dilsizian, Pamela S. Douglas, Joel Dudley, Frederick Epstein, Linda Gillam, Justin Lundbye, Ben McCallister, Jagat Narula, Rajan A.G. Patel, David Reynolds, U. Joseph Schoepf, Partho P. Sengupta, Nishant Shah, Prem Soman, James E. Udelson, Uma S. Valeti, Mary Norine Walsh, R. Parker Ward, W. Guy Weigold, Neil J. Weissman, Richard D. White, David Wolinsky, Timothy C. Wong, William A. Zoghbi
Journal: JACC. Cardiovascular imaging (2016)