tbuckley/cabot-search huggingface dataset:
Abstract OT3-01-01: A phase II study of PD-L1 and CTLA-4 inhibition and immunopharmcogenomics in metastatic breast cancer
Authors: CA Santa-Maria, S Jain, L Flaum, J-H Park, T Kato, L Gross, R Uthe, C Tellez, R Stein, A Rademaker, WJ Gradishar, Y Nakamura, FJ Giles, M Cristofanilli
Journal: Cancer Research (2017)

Abstract Background A hallmark of cancer is its ability to evade the immune system, however, it can be harnessed to detect and destroy cancer cells through inhibition of immune checkpoints such as CTLA-4 and PD-L1. This strategy has complementary and non-redundant mechanisms resulting in immune activation and antitumor synergy; progression free survival benefit has already been demonstrated in melanoma. A critical barrier in developing immunotherapies, however, is the identification of predictive biomarkers of response to therapy. Immunopharmacogenomic biomarkers, such as mutational burden, neoantigen profiles, and T cell receptor sequencing will elucidate the molecular interface between cancer and immune system, and may predict those most likely to benefit. Methods A single arm Phase II study was designed to determine the efficacy of PD-L1 and CTLA-4 inhibition and effects on immunopharmacogenomic dynamics in patients with metastatic breast cancer. The primary endpoint of this proposal is to investigate the response rate of the PD-L1 inhibitor, durvalumab, and the CTLA-4 inhibitor, tremelimumab, in metastatic breast cancer; secondary endpoints will examine the T cell receptor repertoire clonality, tumor mutational burden and neoantigen profiles. A total of 30 patients will be enrolled and treated with durvalumab 1500mg IV and tremelimumab 75mg IV monthly for 4 doses, then durvalumab 750mg every 2 weeks for 18 doses to complete 1 year of therapy with the option to renew therapy for an additional year; biopsies and blood at baseline and 2 months will be collected to assess immunopharmacogenomic biomarkers. Patients are eligible if they have triple negative or ER-positive breast cancer and have progressed on at least one line of chemotherapy and standard endocrine therapy if applicable. This is the first study to investigate immunopharmacogenomic biomarkers of response to dual checkpoint blockade in patients with metastatic breast cancer. Citation Format: Santa-Maria CA, Jain S, Flaum L, Park J-H, Kato T, Gross L, Uthe R, Tellez C, Stein R, Rademaker A, Gradishar WJ, Nakamura Y, Giles FJ, Cristofanilli M. A phase II study of PD-L1 and CTLA-4 inhibition and immunopharmcogenomics in metastatic breast cancer [abstract]. In: Proceedings of the 2016 San Antonio Breast Cancer Symposium; 2016 Dec 6-10; San Antonio, TX. Philadelphia (PA): AACR; Cancer Res 2017;77(4 Suppl):Abstract nr OT3-01-01.
Gender-Dependent Up-Regulation of the VWF-Cleaving metalloprotease ADAMTS-13 in Mice with Obesity and Hypercholesterolemia.
Authors: Anne Liu, Huaizhu Wu, Zhenyin Tao, Hiuwan Choi, Angela Bergeron, Christie M. Ballantyne, Jing-Fei Dong
Journal: Blood (2004)
Multiple Myeloma Oncogene 1 (MUM1)/Interferon Regulatory Factor 4 (IRF4) Upregulates Monokine Induced by Interferon-gamma (MIG) Gene Expression in B-Cell Malignancy.
Authors: Shinsuke Iida, Miyuki Uranishi, Takaomi Sanda, Takashi Ishida, Emi Tajima, Masato Ito, Hirokazu Komatsu, Hiroshi Inagaki, Ryuzo Ueda
Journal: Blood (2004)
Current approaches to increase CAR T cell potency in solid tumors: targeting the tumor microenvironment
Authors: Irene Scarfò, Marcela V. Maus
Journal: Journal for ImmunoTherapy of Cancer (2017)

Chimeric antigen receptor (CAR) T-cell therapy represents a revolutionary treatment for haematological malignancies (i.e. B-ALL). However, the success of this type of treatment has not yet been achieved in solid tumors. One hypothesis is that the immunosuppressive nature of the tumor microenvironment (TME) influences and affects the efficacy of adoptive immunotherapy. Understanding the role of the TME and its interaction with CAR T-cells is crucial to improve the potency of adoptive immunotherapy. In this review, we discuss the strategies and potential combinatorial approaches recently developed in mouse models to enhance the efficacy of CAR T-cells, with particular emphasis on the translational potential of these approaches.
Abstract 2540: Glucagon-Like Peptide-1 Improves Glycemic Control and Preserves Left Ventricular Function in Patients Undergoing Coronary Artery Bypass Grafting with Reduced Requirements for Insulin and Inotropes
Authors: Hakki Bolukoglu, George G Sokos, Judy Germani, Teresa Hentosz, Carol Stolarski, Richard P Shannon
Journal: Circulation (2006)

Background: Increasing evidence suggests that tight glycemic control improves clinical outcomes following coronary artery bypass grafting (CABG). However, the risks of hypoglycemia with insulin res...
Knock-in of Dnmt3a R878H Recapitulates Human Acute Myeloid Leukemia Harboring DNMT3A Mutation and Is Highly Responsive to mTOR Inhibitor Rapamycin
Authors: Yujun Dai, Yueying Wang, Jinyan Huang, Li Xia, Xiaodong Shi, Sai-Juan Chen, Zhu Chen
Journal: Blood (2016)
Comparison of Posttransplant Dermatologic Diseases by Race
Authors: Christina Lee Chung, Kumar S. Nadhan, Christine M. Shaver, Lauren M. Ogrich, Mark Abdelmalek, Carrie Ann Cusack, Gregory E. Malat, Ellen N. Pritchett, Alden Doyle
Journal: JAMA Dermatology (2017)

The risk for skin cancer has been well characterized in white organ transplant recipients (OTRs); however, most patients on the waiting list for organ transplant in the United States are nonwhite. Little is known about cutaneous disease and skin cancer risk in this OTR population.To compare the incidence of cutaneous disease between white and nonwhite OTRs.This retrospective review of medical records included 412 OTRs treated from November 1, 2011, through April 22, 2016, at an academic referral center. Prevalence and characteristics of cutaneous disease were compared in 154 white and 258 nonwhite (ie, Asian, Hispanic, and black) OTRs. Clinical factors of cutaneous disease and other common diagnoses assessed in OTRs included demographic characteristics, frequency and type of cancer, anatomical location, time course, sun exposure, risk awareness, and preventive behavior.Primary diagnosis of malignant or premalignant, infectious, and inflammatory disease.The 412 patients undergoing analysis included 264 men (64.1%) and 148 women (35.9%), with a mean age of 60.1 years (range, 32.1-94.3 years). White OTRs more commonly had malignant disease at their first visit (82 [67.8%]), whereas nonwhite OTRs presented more commonly with infectious (63 [37.5%]) and inflammatory (82 [48.8%]) conditions. Skin cancer was diagnosed in 64 (41.6%) white OTRs and 15 (5.8%) nonwhite OTRs. Most lesions in white (294 of 370 [79.5%]) and Asian (5 of 6 [83.3%]) OTRs occurred in sun-exposed areas. Among black OTRs, 6 of 9 lesions (66.7%) occurred in sun-protected areas, specifically the genitals. Fewer nonwhite than white OTRs reported having regular dermatologic examinations (5 [11.4%] vs 8 [36.4%]) and knowing the signs of skin cancer (11 [25.0%] vs 10 [45.4%]).Early treatment of nonwhite OTRs should focus on inflammatory and infectious diseases. Sun protection should continue to be emphasized in white, Asian, and Hispanic OTRs. Black OTRs should be counseled to recognize the signs of genital human papillomavirus infection. Optimal posttransplant dermatologic care may be determined based on the race or ethnicity of the patients, but a baseline full-skin assessment should be performed in all patients. All nonwhite OTRs should be counseled more effectively on the signs of skin cancer, with focused discussion points contingent on skin type and race or ethnicity.
Time Interval Data in a Pediatric In-Hospital Resuscitation Study—Reply
Authors: Lars W. Andersen, Robert A. Berg, Michael W. Donnino
Journal: JAMA (2017)

Our website uses cookies to enhance your experience. By continuing to use our site, or clicking "Continue," you are agreeing to our Cookie Policy | Continue JAMA 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
Abstract IA13: Imaging drug delivery and nanotherapeutics
Authors: Ralph Weissleder
Journal: Cancer Research (2017)

Abstract Over 180 chemically distinct cancer drugs are currently in clinical use while new nanomaterials, small molecule inhibitors and newer immunotherapeutics are entering clinical trials. Preclinical testing usually involves measuring tumor sizes, survival endpoints, the use of histopathology and measurement of serum biomarkers. Yet, despite all of these advances, preciously little is known on how many of these compounds actually work (or fail) at the single cell level in vivo, what the spatial and temporal heterogeneity is and how efficacy can be improved. The latter is particularly vexing as the majority of patients show suboptimal responses and tumors often relapse within months-years. With the recent development of i) single cell in vivo imaging technology (Nat Commun 2013;4,1504), ii) fluorescent nanoparticles and encapsulated therapeutics (Science Transl Med, 2015;7:314; Nat Commun. 2015;6:8692), iii) in vivo reporters of host response, cell death or DNA damage (ChemMedChem, 2014;9:1131), iv) new computational analysis (Nat Methods, 2015;12:577), and v) armed with new biological insight from feasibility studies we are now able to address important cancer therapeutics questions in ways that were not previously possible. In this presentation I will review imaging approaches for the functional assessment of new therapeutics at the single cell level in vivo, addressing key questions on distribution (pharmacokinetics, PK) and specific cellular response (pharmacodynamics, PD). Citation Format: Ralph Weissleder. Imaging drug delivery and nanotherapeutics. [abstract]. In: Proceedings of the AACR Special Conference on Engineering and Physical Sciences in Oncology; 2016 Jun 25-28; Boston, MA. Philadelphia (PA): AACR; Cancer Res 2017;77(2 Suppl):Abstract nr IA13.
Complications are more common in young people with type 2 diabetes than type 1
Authors: Jacqui Wise
Journal: BMJ (2017)

Almost three quarters of teenagers and young adults with type 2 diabetes have a complication, compared with about one in three with type 1 diabetes, research published in JAMA has found.1

The researchers said that complications and comorbidities were frequent in both groups and called for greater monitoring of young people with diabetes.

The prevalence of type 2 diabetes in children and adolescents has been increasing since the early to mid-1990s, and type 1 diabetes …
Perspectives on Care for the Elderly in China
Authors: Fei Wu, Tomohiro Morita, Akihiko Ozaki
Journal: JAMA Internal Medicine (2017)

Our website uses cookies to enhance your experience. By continuing to use our site, or clicking "Continue," you are agreeing to our Cookie Policy | Continue JAMA Internal Medicine HomeNew OnlineCurrent IssueFor Authors Podcast Publications JAMA JAMA Network Open JAMA Cardiology JAMA Dermatology JAMA Health Forum JAMA Internal Medicine JAMA Neurology JAMA Oncology JAMA Ophthalmology JAMA Otolaryngology–Head & Neck Surgery JAMA Pediatrics JAMA Psychiatry JAMA Surgery Archives of Neurology & Psychiatry (1919-1959) JN Learning / CMESubscribeJobsInstitutions / LibrariansReprints & Permissions Terms of Use | Privacy Policy | Accessibility Statement 2023 American Medical Association. All Rights Reserved Search All JAMA JAMA Network Open JAMA Cardiology JAMA Dermatology JAMA Forum Archive JAMA Health Forum JAMA Internal Medicine JAMA Neurology JAMA Oncology JAMA Ophthalmology JAMA Otolaryngology–Head & Neck Surgery JAMA Pediatrics JAMA Psychiatry JAMA Surgery Archives of Neurology & Psychiatry Input Search Term Sign In Individual Sign In Sign inCreate an Account Access through your institution Sign In Purchase Options: Buy this article Rent this article Subscribe to the JAMA Internal Medicine journal
Infection Complications in 476 Patients with Newly Diagnosed Multiple Myeloma Treated with Lenalidomide or Bortezomib Combinations
Authors: Massimo Offidani, Laura Corvatta, Sara Bringhen, Silvia Gentili, Francesca Gay, Laura Maracci, Mario Boccadoro, Pietro Leoni, Antonio Palumbo
Journal: Blood (2015)
Lineage-Specific Expression and Functional Relevance of MicroRNA Genes in Normal Hematopoiesis.
Authors: Nadia Felli, Elvira Pelosi, Rosanna Botta, Laura Fontana, Valentina Lulli, Giovanna Marziali, Ornella Morsilli, Mauro Valtieri, Lucia Ricci Vitiani, George A. Calin, Chang-Gong Liu, Antonio Sorrentino, Carlo M. Croce, Cesare Peschle
Journal: Blood (2005)
A Randomized Phase II Trial of Dasatinib 100 Mg Vs Imatinib 400 Mg In Newly Diagnosed Chronic Myeloid Leukemia In Chronic Phase (CML-CP): The S0325 Intergroup Trial
Authors: Jerald P. Radich, Kenneth J. Kopecky, Suzanne Kamel-Reid, Wendy Stock, Elisabeth Paietta, Martha Wadleigh, Richard A. Larson, Peter D. Emanuel, Martin S. Tallman, Jeffrey Lipton, Stephen Couban, Michael W. Deininger, Frederick R. Appelbaum, Brian J. Druker
Journal: Blood (2010)
Nicotinamide Mononucleotide, an NAD+ Precursor, Rescues Age-Associated Susceptibility to AKI in a Sirtuin 1–Dependent Manner
Authors: Yi Guan, Su-Rong Wang, Xin-Zhong Huang, Qiong-hong Xie, Yun-Yu Xu, Da Shang, Chuan-Ming Hao
Journal: Journal of the American Society of Nephrology (2017)

The rapid growth of an aging population creates challenges regarding age-related diseases, including AKI, for which both the prevalence and death rate increase with age. The molecular mechanism by which the aged kidney becomes more susceptible to acute injury has not been completely elucidated. In this study, we found that, compared with the kidneys of 3-month-old mice, the kidneys of 20-month-old mice expressed reduced levels of the renal protective molecule sirtuin 1 (SIRT1) and its cofactor NAD + . Supplementation with nicotinamide mononucleotide (NMN), an NAD + precursor, restored renal SIRT1 activity and NAD + content in 20-month-old mice and further increased both in 3-month-old mice. Moreover, supplementation with NMN significantly protected mice in both age groups from cisplatin-induced AKI. SIRT1 deficiency blunted the protective effect of NMN, and microarray data revealed that c-Jun N-terminal kinase (JNK) signaling activation associated with renal injury in SIRT1 heterozygotes. In vitro , SIRT1 attenuated the stress response by modulating the JNK signaling pathway, probably via the deacetylation of a JNK phosphatase, DUSP16. Taken together, our findings reveal SIRT1 as a crucial mediator in the renal aging process. Furthermore, manipulation of SIRT1 activity by NMN seems to be a potential pharmaceutical intervention for AKI that could contribute to the precise treatment of aged patients with AKI.
A centrocyte blood count of a quarter million
Authors: Matthew Behrens, Rajasree P. Chowdry, Saliba Saba, Nakhle S. Saba
Journal: American Journal of Hematology (2017)

A 66 year-old Caucasian male presented with several weeks of fatigue, night sweats, and left upper quadrant abdominal pain. Physical exam revealed pallor and massive hepatosplenomegaly. A complete blood count showed anemia, thrombocytopenia, and marked leukocytosis (268,000/µL). Differential showed an absolute lymphocyte count of 253,840/µL. Peripheral smear revealed marked leukocytosis composed of mature-appearing lymphocytes and smudge cells suggestive of chronic lymphocytic leukemia (Image 1, panel A). However, the majority of the leukocytes had cleaved nuclei (Image 1, panel B) consistent with the appearance of centrocytes. A working diagnosis of follicular lymphoma (FL) was made based on this finding. This was supported by flow cytometry of the peripheral blood and immunohistochemistry on a lymph node (LN) biopsy showing a kappa-restricted monoclonal B-cell population that was positive for CD10, CD19, CD20, CD79a, BCL-2, and BCL-6 and negative for CD3, CD5, CD21, CD23, CD38, and cyclin-D1. The neoplastic follicles in the LN were underlain by follicular dendritic cell networks positive for CD21 and CD23. The Ki-67 stain showed a variable proliferation index averaging 50%-60%. Further, fluorescence in situ hybridization was positive for translocation t(14;18)(q32;q21), and subsequent BCL2 overexpression by immunohistochemistry on the heavily involved bone marrow. A normal pattern was observed for the BCL6 locus. A karyotype showed, in addition to t(14;18), additional material of unknown origin on the distal long arm of chromosome 12. Peripheral smear showing in (A) a marked leukocytosis composed of mature-appearing lymphocytes and smudge cells, and in (B) the cleaved nuclei of the malignant cells consistent with the appearance of centrocytes Centrocytes represent small cells with cleaved nuclei, as opposed to centroblasts, which are larger and have nuclei that are noncleaved.1 Grading of FL is based on this morphology and plays a key role in prognosis and choice of therapy.1 Other morphological variants have also been reported.2 Leukemic phase is an uncommon presentation of FL, reported in 4%-23% of cases but appears to be higher in the Japanese population.1, 3-6 Recent review of literature shows that the absolute lymphocyte count in FL with a leukemic phase is widely variable and ranges from ∼5000 cells/µL to 560,000 cells/µL, with a median of ∼28,000 cells/µL and an average of ∼102,000 cells/µL. Although there is limited data on the clinical outcomes of FL with a leukemic phase, several case series have suggested a more aggressive course and overall worse prognosis compared to “node-only” disease. The latter classically has an indolent course. FL in the leukemic phase can often mimic the presentation of chronic lymphocytic leukemia. A peripheral smear showing the deep angulated clefts that are pathognomonic for centrocytes in the leukemic phase can often be the first unique finding of this alternative diagnosis.
Phase II Study of Low-Dose Pomalidomide in Patients with Myelofibrosis and Significant Anemia (hemoglobin &lt;10g/dL)
Authors: Aditi Shastri, Tapan Kadia, Jorge E. Cortes, Kurt Schroeder, Hagop M. Kantarjian, Srdan Verstovsek
Journal: Blood (2011)
Football nutrition: time for a new consensus?
Authors: James Collins, Alan McCall, Johann Bilsborough, Ron Maughan
Journal: British Journal of Sports Medicine (2017)

Good nutrition choices can support optimal health and performance of footballers. The intake, type, quantity and timing of foods, fluids and supplementation can optimise preparation, performance and recovery of players within and between matches.1 In the fast-paced world of elite football, a one-stop shop resource gathering current best practice and research information would greatly benefit practitioners and players. Expert consensus statements are widely used to improve the quality of player care. Recently, a generic sports nutrition consensus was published1; however, football is different and somewhat unique, and specific nutrition guidelines have not been updated for over a decade.2 

We believe that sports-specific recommendations are needed, and 10 years on we ask ourselves, are these guidelines relevant today? This editorial highlights (1) why an updated football-specific consensus is necessary and (2) how it can benefit the modern-day football practitioner and player.

### Research is moving faster than we can keep up

Like many areas in sports-related research, there has been an exponential increase …
Commentary on the recent international multicentre study (EUVAS) on antineutrophil cytoplasmic antibodies
Authors: Michael Mahler, Marvin Fritzler
Journal: Annals of the Rheumatic Diseases (2017)

Antineutrophil cytoplasmic antibodies (ANCAs)-associated vasculitis (AAV) is a group of potentially life-threatening conditions that require early and accurate diagnosis, most often based on a combination of clinical and serological features.1 Most of the therapeutic modalities have immune-suppressing activity and can result in serious consequences, especially if applied to patients without AAV, such as those with infectious diseases, which may have clinical features that mimic AAV. Because an early and accurate diagnosis of AAV is a clinical imperative, both the differential diagnosis and the working diagnosis leading to urgent initial treatment are critical steps in the clinical care pathway. Even then, refinement of the diagnosis might be required during the clinical course after the initial choice of therapeutic strategies.

In this context and with interest we read the recent article by …
The In Vivo Recovery/Survivaland Pharmacokinetic Properties of Dexamethasone Sodium Phosphate Encapsulated in Autologous Erythrocytes
Authors: Shodeinde Coker, Zbigniew M Szczepiorkowski, Alan H. Seigel, Antonio Ferrari, Luca Benatti, Giovanni Mambrini, Ravi Anand, Richard D. Hartman, Larry J. Dumont
Journal: Blood (2016)
Outcome of Acute Myeloid Leukemia in Children and Young Adults Treated with an Uniform Protocol in Casablanca, Morocco
Authors: Bienvenu Houssou, Mouna Lamchahab, Romaric Massi, Nisrine Khoubila, Siham Cherkaoui, Meryem Qachouh, Mohamed Rachid, Abdallah Madani, Uma H. Athale, Asmaa AQ Quessar
Journal: Blood (2016)