tbuckley/cabot-search huggingface dataset:
Clinicopathologic characteristics and treatment of marginal zone lymphoma of mucosa‐associated lymphoid tissue (MALT lymphoma)
Authors: Markus Raderer, Barbara Kiesewetter, Andrés J. M. Ferreri
Journal: CA A Cancer Journal for Clinicians (2015)

Answer questions and earn CME/CNE Extranodal marginal zone lymphoma of the mucosa‐associated lymphoid tissue (MALT lymphoma) accounts for 7% to 8% of newly diagnosed lymphomas. Because of its association with infectious causes, such as Helicobacter pylori (HP) or Chlamydophila psittaci (CP), and autoimmune diseases, it has become the paradigm of an antigen‐driven malignancy. MALT lymphoma usually displays an indolent course, and watch‐and‐wait strategies are justified initially in a certain percentage of patients. In patients with gastric MALT lymphoma or ocular adnexal MALT lymphoma, antibiotic therapy against HP or CP, respectively, is the first‐line management of choice, resulting in lymphoma response rates from 75% to 80% after HP eradication and from 33% to 65% after antibiotic therapy for CP. In patients who have localized disease that is refractory to antibiotics, radiation is widely applied in various centers with excellent local control, whereas systemic therapies are increasingly being applied, at least in Europe, because of the potentially systemic nature of the disease. Therefore, the objective of this review is to briefly summarize the clinicopathologic characteristics of this distinct type of lymphoma along with current data on management strategies. CA Cancer J Clin 2016;66:152–171. © 2015 American Cancer Society.
Racial Differences in the Use and Outcome of Neoadjuvant Chemotherapy for Breast Cancer: Results From the National Cancer Data Base
Authors: Brigid K. Killelea, Vicky Q. Yang, Shi-Yi Wang, Brandon Hayse, Sarah Mougalian, Nina R. Horowitz, Anees B. Chagpar, Lajos Pusztai, Donald R. Lannin
Journal: Journal of Clinical Oncology (2015)

To explore racial differences in the use and outcome of neoadjuvant chemotherapy for breast cancer.The National Cancer Data Base was queried to identify women with stage 1 to 3 breast cancer diagnosed in 2010 and 2011. Chemotherapy use and rate of pathologic complete response (pCR) was determined for various racial/ethnic groups.Of 278,815 patients with known race and ethnicity, 127,417 (46%) received chemotherapy, and of 121,446 where the timing of chemotherapy was known, 27,300 (23%) received neoadjuvant chemotherapy. Chemotherapy, and neoadjuvant chemotherapy in particular, was given more frequently to black, Hispanic, and Asian women than to white women (P < 0.001). This difference was largely explained by more advanced stage, higher grade tumors, and a greater proportion of triple-negative and human epidermal growth factor receptor 2 (HER2)-positive tumors in these women. Of 17,970 patients with known outcome, 5,944 (33%) had a pCR. No differences in response rate for estrogen receptor (ER)/progesterone receptor (PR)-positive tumors were found, but compared with white women, black but not Hispanic or Asian women had a lower rate of pCR for ER/PR-negative, HER2-positive (43% v 54%, P = 0.001) and triple-negative tumors (37% v 43%, P < 0.001). This difference persisted when adjusted for age, clinical T stage, clinical N stage, histology, grade, comorbidity index, facility type, geographic region, insurance status, and census-derived median income and education for the patient's zip code (odds ratio, 0.84; 95% CI, 0.77 to 0.93).Neoadjuvant chemotherapy is given more frequently to black, Hispanic, and Asian women than to white women. Black women have a lower likelihood of pCR for triple-negative and HER2-positive breast cancer. Whether this is due to biologic differences in chemosensitivity or to treatment or socioeconomic differences that could not be adjusted for is unknown.
Decrease of hypervirulent Clostridium difficile PCR ribotype 027 in the Netherlands
Authors: M P Hensgens, A Goorhuis, D  W Notermans, B H van Benthem, E  J Kuijper
Journal: Eurosurveillance (2009)

After the first outbreaks of Clostridium difficile PCR ribotype 027 (North American pulsed-field type 1, restriction endonuclease analysis group BI) in the Netherlands in 2005, a national surveillance programme for C. difficile infection (CDI) was started. Furthermore, national guidelines were developed to rapidly recognise type 027 infections and prevent further spread. The mean incidence of CDI measured in 14 hospitals remained stable throughout the years: an incidence of 18 per 10,000 admissions was seen in 2007 and 2008. Between April 2005 and June 2009 a total of 2,788 samples were available for PCR ribotyping. A decrease was seen in the number and incidence of type 027 after the second half of 2006. In the first half of 2009, the percentage of type 027 isolates among all CDI decreased to 3.0%, whereas type 001 increased to 27.5%. Type 014 was present in 9.3% of the isolates and C. difficile type 078 slightly increased to 9.1%. We conclude that currently there is a significant decrease in type 027-associated CDI in the Netherlands.
Medical Directive for Urinary Catheter Removal by Nurses on General Medical Wards
Authors: Jerome A. Leis, Carla Corpus, Armin Rahmani, Barbara Catt, Brian M. Wong, Sandra Callery, Mary Vearncombe
Journal: JAMA Internal Medicine (2015)

Medical Directive for Urinary Catheter Removal by Nurses on General Medical WardsLeaving a urinary catheter (UC) in place without indication has been identified as one of "Five Things Physicians and Patients Should Question" by the Society of Hospital Medicine and the Canadian Society of Internal Medicine. 1,2On a busy general medical (GM) ward, delays in reassessment of UCs can lead to catheter-associated urinary tract infection (CAUTI). 3Interventions aimed at physicians reduce unnecessary UC use, 4 but empowering nurses to remove UCs through the use of medical directives remains an underused strategy. 5Methods | A controlled before-and-after study in GM patients admitted to a large academic hospital was performed to evalu-Figure.Postcatheter Care Algorithm A medical directive for nurses to remove urinary catheters among general medical patients lacking prespecified exclusion criteria, and provide postcatheter care.jamainternalmedicine.com
Radiation Dose-Response Relationship for Risk of Coronary Heart Disease in Survivors of Hodgkin Lymphoma
Authors: Frederika A. van Nimwegen, Michael Schaapveld, David J. Cutter, Cècile P.M. Janus, Augustinus D.G. Krol, Michael Hauptmann, Karen Kooijman, Judith Roesink, Richard van der Maazen, Sarah C. Darby, Berthe M.P. Aleman, Flora E. van Leeuwen
Journal: Journal of Clinical Oncology (2015)

Cardiovascular diseases are increasingly recognized as late effects of Hodgkin lymphoma (HL) treatment. The purpose of this study was to identify the risk factors for coronary heart disease (CHD) and to quantify the effects of radiation dose to the heart, chemotherapy, and other cardiovascular risk factors.We conducted a nested case-control study in a cohort of 2,617 5-year HL survivors, treated between 1965 and 1995. Cases were patients diagnosed with CHD as their first cardiovascular event after HL. Detailed treatment information was collected from medical records of 325 cases and 1,204 matched controls. Radiation charts and simulation radiographs were used to estimate in-field heart volume and mean heart dose (MHD). A risk factor questionnaire was sent to patients still alive.The median interval between HL and CHD was 19.0 years. Risk of CHD increased linearly with increasing MHD (excess relative risk [ERR]) per Gray, 7.4%; 95% CI, 3.3% to 14.8%). This results in a 2.5-fold increased risk of CHD for patients receiving a MHD of 20 Gy from mediastinal radiotherapy, compared with patients not treated with mediastinal radiotherapy. ERRs seemed to decrease with each tertile of age at treatment (ERR/Gy(<27.5years), 20.0%; ERR/Gy(27.5-36.4years), 8.8%; ERR/Gy(36.5-50.9years), 4.2%; P(interaction) = .149). Having ≥ 1 classic CHD risk factor (diabetes mellitus, hypertension, or hypercholesterolemia) independently increased CHD risk (rate ratio, 1.5; 95% CI, 1.1 to 2.1). A high level of physical activity was associated with decreased CHD risk (rate ratio, 0.5; 95% CI, 0.3 to 0.8).The linear radiation dose-response relationship identified can be used to predict CHD risk for future HL patients and survivors. Appropriate early management of CHD risk factors and stimulation of physical activity may reduce CHD risk in HL survivors.
Localization and Antibiotic Management of Urinary Tract Infection
Authors: L S T Fang, N E Tolkoff-Rubin, R H Rubin
Journal: Annual Review of Medicine (1979)

Postpartum depression (PPD) is common, disabling, and treatable. The strongest risk factor is a history of mood or anxiety disorder, especially having active symptoms during pregnancy. As PPD is one of the most common complications of childbirth, it is ...Read More
Jump in winter deaths last year is blamed on ineffective flu vaccine
Authors: Zosia Kmietowicz
Journal: BMJ (2015)

Excess deaths in England and Wales in 2014-15 were the highest for 15 years, the Office for National Statistics has reported, largely because of an ineffective flu vaccine.1

An estimated 43 900 excess winter deaths occurred in England and Wales from December to March 2014-15, the highest number since 1999-2000. Altogether, 27% more people died in the …
Counselling has much to offer patients
Authors: P. Sugarman, G. Addie
Journal: BMJ (1996)

EDITOR,—Simon Wessely's reactionary assault on counselling expresses a hostility that is widespread among psychiatrists.1 Wessely urges the use of directive psychological treatment for specific syndromes that has been proved in comparative trials and is delivered by defined staff. He cites obsessive-compulsive and phobic disorders as such specific syndromes. He mentions anxiety and depression and sexual problems, but not bereavement or difficulties with relationships. He dismisses counselling for emotional problems (using …
Oncologists' reluctance to accrue patients onto clinical trials: an Illinois Cancer Center study.
Authors: A B Benson, J P Pregler, J A Bean, A W Rademaker, B Eshler, K Anderson
Journal: Journal of Clinical Oncology (1991)

Clinical trials are recognized as the standard of care for the cancer patient, and the randomized, controlled trial represents the most definitive method to determine the effectiveness or ineffectiveness of a cancer treatment. However, less than 3% of all eligible patients enter a clinical trial. Of the 437 physician members of the Illinois Cancer Center (ICC), 244 responded to a survey designed to determine factors that present a significant barrier to entering patients on clinical trials. Rigid protocol design was the primary deterrent to accrual, especially for medical oncologists. Surgeons, radiation oncologists, and medical oncologists differed with respect to several factors, including willingness to seek a clinical trial, tendency to treat patients off study, quality-of-life issues, and the belief that trials were too excessive in time commitment (P less than .05). Compared with hospital-based physicians, community oncologists had fewer patients on trial, were more likely to enter patients on the basis of age, and were more concerned about aspects of informed consent and the financial burden of a trial (P less than .01). One third of the physicians never pursued a clinical trial because of conflict with the priorities of individual care and excessive follow-up time. Fourteen percent indicated that they discouraged patients from participating in a clinical trial due to the risk of a patient receiving a placebo and patient follow-up requirements (P less than .05). Subgroups of physicians differ in their reluctance to accrue patients, and there are clusters of beliefs expressed by physicians concerning their clinical trial activity. Current conduct of clinical trials needs to be reassessed, and intervention studies are required to determine the best methodology to alter physician reluctance to pursue clinical trials.
Clinical Impact of Additional Cytogenetic Aberrations, <i>cKIT</i> and <i>RAS</i> Mutations, and Treatment Elements in Pediatric t(8;21)-AML: Results From an International Retrospective Study by the International Berlin-Frankfurt-Münster Study Group
Authors: Kim Klein, Gertjan Kaspers, Christine J. Harrison, H. Berna Beverloo, Ardine Reedijk, Mathilda Bongers, Jacqueline Cloos, Andrea Pession, Dirk Reinhardt, Martin Zimmerman, Ursula Creutzig, Michael Dworzak, Todd Alonzo, Donna Johnston, Betsy Hirsch, Michal Zapotocky, Barbara De Moerloose, Alcira Fynn, Vincent Lee, Takashi Taga, Akio Tawa, Anne Auvrignon, Bernward Zeller, Erik Forestier, Carmen Salgado, Walentyna Balwierz, Alexander Popa, Jeffrey Rubnitz, Susana Raimondi, Brenda Gibson
Journal: Journal of Clinical Oncology (2015)

This retrospective cohort study aimed to determine the predictive relevance of clinical characteristics, additional cytogenetic aberrations, and cKIT and RAS mutations, as well as to evaluate whether specific treatment elements were associated with outcomes in pediatric t(8;21)-positive patients with acute myeloid leukemia (AML).Karyotypes of 916 pediatric patients with t(8;21)-AML were reviewed for the presence of additional cytogenetic aberrations, and 228 samples were screened for presence of cKIT and RAS mutations. Multivariable regression models were used to assess the relevance of anthracyclines, cytarabine, and etoposide during induction and overall treatment. End points were the probability of achieving complete remission, cumulative incidence of relapse (CIR), probability of event-free survival, and probability of overall survival.Of 838 patients included in final analyses, 92% achieved complete remission. The 5-year overall survival, event-free survival, and CIR were 74%, 58%, and 26%, respectively. cKIT mutations and RAS mutations were not significantly associated with outcome. Patients with deletions of chromosome arm 9q [del(9q); n = 104] had a lower probability of complete remission (P = .01). Gain of chromosome 4 (+4; n = 21) was associated with inferior CIR and survival (P < .01). Anthracycline doses greater than 150 mg/m(2) and etoposide doses greater than 500 mg/m(2) in the first induction course and high-dose cytarabine 3 g/m(2) during induction were associated with better outcomes on various end points. Cumulative doses of cytarabine greater than 30 g/m(2) and etoposide greater than 1,500 mg/m(2) were associated with lower CIR rates and better probability of event-free survival.Pediatric patients with t(8;21)-AML and additional del(9q) or additional +4 might not be considered at good risk. Patients with t(8;21)-AML likely benefit from protocols that have high doses of anthracyclines, etoposide, and cytarabine during induction, as well as from protocols comprising cumulative high doses of cytarabine and etoposide.
Paediatric necrolytic migratory erythema as a presenting sign of glucagonoma syndrome
Authors: A.J. Luber, L.S. Ackerman, K.S. Culpepper, C.M. Buschmann, L.J. Koep
Journal: British Journal of Dermatology (2015)

Glucagonoma syndrome is an extremely rare pancreatic neuroendocrine tumour often associated with necrolytic migratory erythema. While glucagonomas are neoplasms of adulthood, we report the first case in a paediatric patient. We present the case of a 15-year-old girl with a 4-year history of a rash, consistent with necrolytic migratory erythema, found to have a localized glucagonoma. Immediately following resection of the tumour, there was complete resolution of her rash and systemic symptoms. Detection of the cutaneous rash of necrolytic migratory erythema can aid in the early diagnosis of a glucagonoma, as well as the prevention of metastatic disease. To our knowledge, this is the first reported paediatric patient with glucagonoma syndrome.
TGM2: A Cell Surface Marker in Esophageal Adenocarcinomas
Authors: Deborah T. Leicht, Tasneem Kausar, Zhuwen Wang, Daysha Ferrer-Torres, Thomas D. Wang, Dafydd G. Thomas, Jules Lin, Andrew C. Chang, Lin Lin, David G. Beer
Journal: Journal of Thoracic Oncology (2014)
Transcriptional Regulation of T Cell Receptor Genes
Authors: J M Leiden
Journal: Annual Review of Immunology (1993)

The diverse lineages of the mammalian hematopoietic system including both B and T lymphocytes are derived from a single mesodermal progenitor, the pluripotent bone marrow stem cell. The coordinate transcriptional regulation of sets of lineage-specific genes is one of the important molecular mechanisms underlying hematopoietic lineage determination and differentiation. The immunoglobulin and T cell receptor (TCR) genes have been used as model systems to study lineage-specific transcriptional regulation during lymphoid development. This review summarizes our current understanding of the regulation of TCR gene expression during thymocyte ontogeny. Expression of each of the TCR genes is controlled by T cell-specific transcriptional enhancers that bind partially overlapping sets of ubiquitous and lymphoid-specific transcription factors. These include members of both the ATF/CREB family of basic-leucine zipper proteins and the Ets protooncogene family, as well as the T cell-specific zinc finger transcription factor, GATA-3, and the T cell-specific high mobility group proteins TCF-1 and TCF-1 alpha/LEF-1. The identification of binding sites for these same transcription factors in a number of additional T cell-specific genes suggests that they may play important roles in the coordinate regulation of gene expression that specifies the development of the T cell lineages. Recent studies of the TCR alpha and gamma genes have suggested that negative regulatory elements of transcriptional silencers may also play an important role in controlling the lineage-specific expression of these genes. On going studies are designed to clarify the role of each of the TCR enhancer binding proteins in regulating T cell development in vivo, to more precisely define the interactions between the TCR enhancer binding proteins, and to elucidate the molecular mechanisms underlying transcriptional silencer activity.
siRNA delivered by EGFR-specific scFv sensitizes EGFR-TKI-resistant human lung cancer cells
Authors: Yuan Lu, Li Liu, Yuan Wang, Fakai Li, Jian Zhang, Mingxiang Ye, Hu Zhao, Xiang Zhang, Mi Zhang, Jing Zhao, Bo Yan, Angang Yang, Huasong Feng, Rui Zhang, Xinling Ren
Journal: Biomaterials (2015)

The overexpression of epidermal growth factor receptor (EGFR) is closely associated with a poor outcome in non-small cell lung cancer (NSCLC), and EGFR is an ideal biomarker for the targeted therapy of NSCLC. Although patients with EGFR-activating mutations respond to EGFR tyrosine kinase inhibitors (EGFR-TKIs), they eventually acquire resistance, which typically results from a secondary EGFR mutation or the activation of other signaling pathways. Novel approaches to overcome or prevent EGFR-TKI resistance are clinically important. In this study, we developed an EGFR-scFv-arginine nonamer peptide fusion protein, s-9R, as an siRNA carrier. Here, we show that s-9R effectively and specifically delivers EGFR-siRNAs, KRAS-siRNA and MET-siRNA into NSCLC cells and silences the expression of target genes. The sensitivity of NSCLC cells to gefitinib was restored after treatment with the s-9R/siRNA complex, and the apoptosis rates of the treated cells were significantly higher than those of the control groups. Furthermore, the co-administration of s-9R/siRNA and gefitinib successfully suppressed the progression of H1975 xenograft tumors and extended the life span of tumor-bearing nude mice. Collectively, the results of this study provide not only a new scFv derivative for delivering siRNA into EGFR-overexpressing, TKI-resistant NSCLC cells but also a novel method for overcoming TKI resistance.
Pharmacokinetic and pharmacodynamic analysis of fluorouracil during 72-hour continuous infusion with and without dipyridamole.
Authors: D L Trump, M J Egorin, A Forrest, J K Willson, S Remick, K D Tutsch
Journal: Journal of Clinical Oncology (1991)

During a phase I trial of 3-day simultaneous continuous intravenous infusions of varying doses of fluorouracil (5FUra) and 7.7 mg/kg/d of dipyridamole, we examined the relationships between 5FUra dose and steady-state plasma concentration (Css) and the percentage reduction in WBCs, as well as the percentage frequency of stomatitis. The 5FUra was administered at doses ranging from 185 mg/m2/d times three to 3,600 mg/m2/d times three. In 42 patients, 86 cycles of 5FUra plus dipyridamole and 28 cycles of 5FUra alone were analyzed. The Css of 5FUra varied even within the same dose level. When patients receiving the same 5FUra dose were considered, the interpatient coefficient of variation of 5FUra Css in cycles of 5FUra plus dipyridamole was 23% +/- 4.2%. For courses of 5FUra alone, the coefficient of variation of 5FUra was 15.6% +/- 6.5%. When the occurrence of any degree of stomatitis was related to the Css 5FUra, with patients grouped in cohorts of 2-mumol/L increments, the following equations accurately described the frequency of stomatitis: for 5FUra plus dipyridamole, percentage frequency of stomatitis = 100(1-e-0.114Css), r2 = 0.88; for 5FUra alone, percentage frequency stomatitis = 100(1-e0.122Css), r2 = 0.80. When 5FUra dose was substituted for Css, these relationships were as follows: percentage frequency of stomatitis = 100(1-e-0.00031 [dose]), r2 = 0.85; and percentage frequency of stomatitis = 100(1-e-0.00051 [dose]), r2 = 0.80. When the relationship between the percentage reduction in WBC and Css 5FUra was examined, statistically significant relationships were also apparent: for 5FUra plus dipyridamole, percentage reduction in WBC = 100(1-e-0.085Css), r2 = 0.46; for 5FUra alone, percentage reduction in WBC = 100(1-e-0.060Css), r2 = 0.61. When 5FUra dose was substituted for Css, these relatinships were as follows: percentage reduction in WBC = 100(1-e-0.00023 [dose]), r2 = 0.40; percentage reduction in WBC = 100(1-e-0.00024 [dose]), r2 = 0.65. The relationship between either Css 5FUra or dose 5FUra and either stomatitis or myelosuppression were also well described by the modified Hill equation (J Theor Biol 20:171-201, 1968). These analyses indicate that it should be possible to develop therapeutic regimens wherein 5FUra is administered to achieve a targeted Css determined by the risk and severity of toxicity deemed acceptable.
TGase 2 Induces Allergic Asthma by up-Regulating IgE and Mediators in Cross-Talk of B and Mast Cells Via CD40/CD40L in Mice
Authors: Jai Youl Ro, Gwan Ui Hong, Bum Soo Park, Nam Goo Kim, Young Min Ahn
Journal: Journal of Allergy and Clinical Immunology (2013)
The Role of the T3/Antigen Receptor Complex in T-Cell Activation
Authors: A Weiss, J Imboden, K Hardy, B Manger, C Terhorst, J Stobo
Journal: Annual Review of Immunology (1986)

Exhausted CD8 T (Tex) cells are a distinct cell lineage that arise during chronic infections and cancers in animal models and humans. Tex cells are characterized by progressive loss of effector functions, high and sustained inhibitory receptor expression, ...Read More
Telaprevir-based therapy for treatment of HIV-1 and hepatitis C virus co-infected patients: An early access programme
Authors: Andrea Gori, Manuela Doroana, Oksana Chernova, Jürgen K. Rockstroh, Denes Banhegyi, Colm Bergin, Gabriella Verucchi, Chris Liu, Ralph DeMasi, Blanca Hadacek, Mark Nelson
Journal: Journal of Infection (2015)