tbuckley/cabot-search huggingface dataset:
Phase II, single stage, cohort expansion study of MK-2206 in recurrent endometrial serous cancer.
Authors: Panagiotis Konstantinopoulos, Vicky Makker, William Thomas Barry, Joyce Liu, Neil S. Horowitz, Michael J. Birrer, L. Austin Doyle, Suzanne T. Berlin, Christin Whalen, Paul Van Hummelen, Robert L. Coleman, Carol Aghajanian, Gordon B. Mills, Ursula Matulonis, Shannon Neville Westin, Andrea P. Myers
Journal: Journal of Clinical Oncology (2014)

5515 Background: Although PTEN mutations or loss of PTEN expression are uncommon in endometrial serous carcinomas, approximately half of these tumors harbor PIK3CA mutations and/or amplification of PIK3CA. A Phase II, 2-stage, 2-arm PIK3CA mutation stratified trial of MK-2206 (an allosteric inhibitor of AKT) in recurrent or advanced endometrial cancer showed that all patients with 6 months progression free survival (PFS) had serous histology, leading to an expansion cohort in patients with endometrial serous tumors. Methods: Eligible patients had recurrent or advanced high grade endometrial carcinoma with a serous component. Up to 2 prior chemo lines were permitted; prior treatment with PI3K/MTOR inhibitors was not allowed. All patients were treated with MK-2206 135mg QW; dose was amended from 200mg QW to 135mg QW during the initial patient cohort because of skin toxicity. Primary objective was to evaluate the efficacy of MK-2206 using a composite endpoint of complete and partial response by RECIST 1.1 and PFS of ≥6 months. A target sample size of 14 patients was planned to allow greater than 80% power to reject a null rate of 10% if the true rate of clinical benefit is 36%, when using a binomial exact test with a one-sided alpha < 0.05. If 4 or more responses were seen among the 14 subjects, then the null hypothesis would be rejected to conclude sufficient efficacy for further investigation of MK-2206. Results: 14 patients were enrolled. There were no grade ≥4 toxicities. Potentially drug related grade 3 toxicities (rash, diarrhea, and anemia) were seen in 3 patients (21%). 10 (71%) patients developed disease progression without meeting any of the efficacy endpoints. The remaining 4 patients are currently on study; two (14%) have met the 6 month PFS endpoint with ongoing decrease in the sum of their target lesions of 27.5% and 21.8% from baseline respectively; the other 2 are on cycles 5 and 2 respectively. Updated results will be presented at the time of the meeting. Conclusions: MK-2206 activity has been detected in a fraction of uterine serous cancers. Translational studies including targeted exome sequencing and copy number analysis of PI3KCA are ongoing. We expect to know whether the goal of 4 responses is reached in the next 4 months. Clinical trial information: NCT01312753.
A Comparison of the Effects of 4-Amino-N10-Methyl-Pteroylglutamic Acid and 2,6-Diaminopurine upon Sensitive and Resistant Sublines of a Strain of Mouse Leukemia
Authors: J. H. BURCHENAL, L. F. WEBBER, G. M. MEIGS, J. L. BIEDLER
Journal: Blood (1951)
Screening for Prostate Cancer: Recommendation and Rationale
Journal: Annals of Internal Medicine (2002)

This statement summarizes the current U.S. Preventive Services Task Force (USPSTF) recommendations on screening for prostate cancer and updates the 1996 recommendations on this topic. The complete USPSTF recommendation and rationale statement on this topic, which includes a brief review of the supporting evidence, is available through the USPSTF Web site (www.preventiveservices.ahrq.gov), the National Guideline Clearinghouse (www.guideline.gov), and in print through the Agency for Healthcare Research and Quality Publications Clearinghouse (telephone, 800-358-9295; e-mail, ahrqpubs@ahrq.gov). The complete information on which this statement is based, including tables and references, is available in the accompanying article in this issue and in the summary of the evidence and systematic evidence review on the Web sites already mentioned.
Metastatic thyroid cancer occurring as an unknown primary lesion: the role of F-18 FDG positron emission tomography.
Authors: FAUT DEDE, NYIMAS YULISA AJOEDI, SELIM ANSARI, SUMAN JANA, SHERIF HEIBA, HUSSEIN ABDEL-DAYEM
Journal: Clinical Nuclear Medicine (2001)

Thyroid cancer can appear as metastatic disease of an unknown primary origin, and fluorine-18 fluorodeoxyglucose (F-18 FDG) positron emission tomographic (PET) studies are helpful in the workup evaluation of these patients. The authors describe two patients who had metastatic disease from an unknown primary lesion. F-18 FDG PET studies played an important role in localizing the primary malignant site in the thyroid gland. The utility of F-18 FDG imaging in decreasing the number of procedures, cost, and inconvenience to patients is shown clearly in both cases.
Myocardial Infarction and Estrogen Therapy in Premenopausal Women
Authors: L Rosenberg, B Armstrong, H Jick
Journal: New England Journal of Medicine (1976)

This letter was written in response to the paper by Mann et al. (British Medical Journal 2: 241-245, 1975) which reported an association between oral contraceptive (OC) use and acute myocardial infarction. Rosenberg et al. found that among 34 patients with myocardial infarction, 4 were current users of OCs and 2 used other estrogen-containing drugs. Among 1213 reference women the use was 79 and 26, respectively. The "relative risk" for OC users was 1.9 (95% confidence interval) and for other estrogen users it was 2.8 as compared with nonusers. When standardized for age these estimates became 2.2 and 2.1 and when standardized for the effects of cigarette smoking, history of hypertension, angina, and/ or diabetes the summary rate-ratio estimate for OC users decreased to 1.3 and left essentially unchanged the estimate for other estrogen users. These results are compatible with a modest increase, if any, in risk of myocardial infarction in premenopausal women associated with estrogen use, such as that reported by Mann et al.
A Possibility of Distinction Between Normal and Neoplastic Cells Through Transplantation Into Chick Blastoderms2
Authors: M. Mareel, L. Vakaet, L. de Ridder
Journal: JNCI Journal of the National Cancer Institute (1973)

Transplantation of certain types of cells and tissues into young chick blastoderms suggested a new method for distinguishing between normal and cancer cells. Different kinds of neoplastic and non-neoplastic cells and tissues were transplanted into defects of the lower layer of stage-4 blastoderms. Histologic examination of the blastoderms after 24 hours' incubation showed the lower layer was completely repaired at the level of certain types of non-neoplastic grafts; on the contrary, repair of the lower layer was inhibited by certain types of neoplastic grafts. Interference of neoplastic cells with migration of cells of the lower layer is proposed as the mechanism responsible for such inhibition. The experimental device might be useful as a diagnostic tool.
Abstract B36: In vivo laser-based imaging of the human fallopian tube for future cancer detection.
Authors: Elizabeth M. Swisher, C. David Melville, Richard S. Johnston, Kathy Agnew, Seine Chiang, Eric J. Seibel
Journal: Clinical Cancer Research (2016)

Abstract Inherited mutations in BRCA1 and BRCA2 cause a 20-50% lifetime risk of ovarian, fallopian tubel, or peritoneal carcinoma. Clinical recommendations for these high-risk women include the prophylactic removal of the ovaries and fallopian tubes by age 40 after child-bearing. Recent findings suggest that many presumed ovarian or peritoneal carcinomas arise in fallopian tube epithelium. Although survival rate is &amp;gt;90% when ovarian cancer is detected early (Stage_I), 70% of women have advanced disease (Stage_III/IV) at presentation when survival is less than 30%. Over the years, effective early detection of ovarian cancer has remained elusive, possibly because screening techniques have mistakenly focused on the ovary as the origin of ovarian carcinoma. Unlike ovaries, the fallopian tubes are amenable to direct visual imaging without invasive surgery, using access through the uterine cervix. To develop future screening protocols, we investigated using our 1.2-mm diameter, forward-viewing, scanning fiber endoscope (SFE) to image luminal surfaces of the fallopian tube before laparoscopic surgical removal. Three anesthetized human subjects participated in our protocol development which eventually led to 70-80% of the length of fallopian tubes being imaged in scanning reflectance, using red (632nm), green (532nm), and blue (442nm) laser light. A hysteroscope with saline uterine distention was used to locate the tubal ostia. To facilitate passage of the SFE through the interstitial portion of the fallopian tube, an introducer catheter was inserted 1-cm through each ostia. During insertion, saline was flushed to reduce friction and provide clearer viewing. This is likely the first high-resolution intraluminal visualization of fallopian tubes Citation Format: Elizabeth M. Swisher, C. David Melville, Richard S. Johnston, Kathy Agnew, Seine Chiang, Eric J. Seibel. In vivo laser-based imaging of the human fallopian tube for future cancer detection. [abstract]. In: Proceedings of the AACR Special Conference on Advances in Ovarian Cancer Research: Exploiting Vulnerabilities; Oct 17-20, 2015; Orlando, FL. Philadelphia (PA): AACR; Clin Cancer Res 2016;22(2 Suppl):Abstract nr B36.
Dual Diagnostic Role of 123I-MIBG Scintigraphy in Inverted-Takotsubo Pattern Cardiomyopathy
Authors: Olivier Humbert, Karim Stamboul, Aurélie Gudjoncik, Salim Kanoun, Carole Richard, Alexandre Cochet, Yves Cottin
Journal: Clinical Nuclear Medicine (2015)

We highlight the dual role of I-MIBG scintigraphy in inverted-Takotsubo pattern cardiomyopathy, the diagnosis of which is sometimes challenging: Firstly, I-MIBG scintigraphy can show myocardial sympathetic dysfunction (low I-MIBG uptake) in the hypokinetic basal segments, sparing the left ventricle apex. It is helpful in the imaging diagnosis of inverted-Takotsubo pattern cardiomyopathy and confirms that acute dysfunction of myocardial sympathetic nerve endings occurs with this cardiomyopathy. Secondly, I-MIBG scintigraphy is an accurate imaging examination to detect and localize pheochromocytoma; it can help in the search for an endogenous cause of this adrenergic stress-related cardiomyopathy.
Phenytoin treatment of the binge-eating syndrome
Authors: B M Wermuth, K L Davis, L E Hollister, A J Stunkard
Journal: American Journal of Psychiatry (1977)

Nineteen subjects completed a 12-week double-blind crossover study comparing phenytoin with placebo in the treatment of severe binge eating. In the placebophenytoin sequence the number of binges decreased during phenytoin treatment from both placebo and pretreatment levels. However, in the phenytoin-placebo sequence, not only did phenytoin reduce the number of binges from pretreatment levels, but there was no reversal of this effect during the placebo period. This sequential effect was unexpected and is still unexplained. The mechanism of phenytoin action and the significance of EEG abnormalities found in 7 of the subjects remain uncertain.
Effects of a Psychological Internet Intervention in the Treatment of Mild to Moderate Depressive Symptoms: Results of the EVIDENT Study, a Randomized Controlled Trial
Authors: Jan Philipp Klein, Thomas Berger, Johanna Schröder, Christina Späth, Björn Meyer, Franz Caspar, Wolfgang Lutz, Alice Arndt, Wolfgang Greiner, Viola Gräfe, Martin Hautzinger, Kristina Fuhr, Matthias Rose, Sandra Nolte, Bernd Löwe, Gerhard Andersson, Eik Vettorazzi, Steffen Moritz, Fritz Hohagen
Journal: Psychotherapy and Psychosomatics (2016)

&lt;b&gt;&lt;i&gt;Background:&lt;/i&gt;&lt;/b&gt; Mild to moderate depressive symptoms are common but often remain unrecognized and treated inadequately. We hypothesized that an Internet intervention in addition to usual care is superior to care as usual alone (CAU) in the treatment of mild to moderate depressive symptoms in adults. &lt;b&gt;&lt;i&gt;Methods:&lt;/i&gt;&lt;/b&gt; This trial was controlled, randomized and assessor-blinded. Participants with mild to moderate depressive symptoms (Patient Health Questionnaire, PHQ-9, score 5-14) were recruited from clinical and non-clinical settings and randomized to either CAU or a 12-week Internet intervention (Deprexis) adjunctive to usual care. Outcomes were assessed at baseline, 3 months (post-assessment) and 6 months (follow-up). The primary outcome measure was self-rated depression severity (PHQ-9). The main analysis was based on the intention-to-treat principle and used linear mixed models. &lt;b&gt;&lt;i&gt;Results:&lt;/i&gt;&lt;/b&gt; A total of 1,013 participants were randomized. Changes in PHQ-9 from baseline differed signi&amp;#xFB01;cantly between groups (t&lt;sub&gt;825&lt;/sub&gt; = 6.12, p &lt; 0.001 for the main effect of group). The post-assessment between-group effect size in favour of the intervention was &lt;i&gt;d&lt;/i&gt; = 0.39 (95% CI: 0.13-0.64). It was stable at follow-up, with &lt;i&gt;d&lt;/i&gt; = 0.32 (95% CI: 0.06-0.69). The rate of participants experiencing at least minimally clinically important PHQ-9 change at the post-assessment was higher in the intervention group (35.6 vs. 20.2%) with a number needed to treat of 7 (95% CI: 5-10). &lt;b&gt;&lt;i&gt;Conclusions:&lt;/i&gt;&lt;/b&gt; The Internet intervention examined in this trial was superior to CAU alone in reducing mild to moderate depressive symptoms. The magnitude of the effect is clinically important and has public health implications.
Clonotypic Diversification of Intratumoral T Cells Following Sipuleucel-T Treatment in Prostate Cancer Subjects
Authors: Nadeem Sheikh, Jason Cham, Li Zhang, Todd DeVries, Simon Letarte, Jeff Pufnock, David Hamm, James Trager, Lawrence Fong
Journal: Cancer Research (2016)

Abstract Sipuleucel-T is an autologous cellular therapy for asymptomatic, or minimally symptomatic, metastatic castrate-resistant prostate cancer, designed to stimulate an immune response against prostate cancer. In a recent clinical trial (NCT00715104), we found that neoadjuvant sipuleucel-T increased the number of activated T cells within the tumor microenvironment. The current analysis examined whether sipuleucel-T altered adaptive T-cell responses by expanding pre-existing T cells or by recruiting new T cells to prostate tissue. Next-generation sequencing of the T-cell receptor (TCR) genes from blood or prostate tissue was used to quantitate and track T-cell clonotypes in these treated subjects with prostate cancer. At baseline, there was a significantly greater diversity of circulating TCR sequences in subjects with prostate cancer compared with healthy donors. Among healthy donors, circulating TCR sequence diversity remained unchanged over the same time interval. In contrast, sipuleucel-T treatment reduced circulating TCR sequence diversity versus baseline as measured by the Shannon index. Interestingly, sipuleucel-T treatment resulted in greater TCR sequence diversity in resected prostate tissue in sipuleucel-T–treated subjects versus tissue of nonsipuleucel-T–treated subjects with prostate cancer. Furthermore, sipuleucel-T increased TCR sequence commonality between blood and resected prostate tissue in treated versus untreated subjects with prostate cancer. The broadening of the TCR repertoire within the prostate tissue supports the hypothesis that sipuleucel-T treatment facilitates the recruitment of T cells into the prostate. Our results highlight the importance of assessing T-cell response to immunotherapy both in the periphery and in tumor tissue. Cancer Res; 76(13); 3711–8. ©2016 AACR.
German insurers call for central database of complaints against doctors
Authors: Ned Stafford
Journal: BMJ (2016)

Germany’s public health insurers—who cover more than 90% of the population—have called for the government to adopt measures that would require health professionals to report all incidents of medical malpractice and create a central transparent database for collection and evaluation of the data.

Despite enactment in 2013 of a new patient rights law, Germany still has no central collection point for allegations of malpractice, with cases primarily investigated by regional medical associations, by insurance companies, or in the courts. Experts say that many alleged cases of malpractice are never recorded.

One of the appeals for mandatory malpractice reporting and a central database came from the Medical Advisory …
Abstract 280: Cardiac Disease Status Dictates Functional mRNA Targeting Profiles of Individual microRNAs
Authors: Scot J Matkovich, Gerald W Dorn, Tiffani C Grossenheider, Peter J Hecker
Journal: Circulation Research (2015)

Background: Gain- and loss-of-function experiments have demonstrated that microRNAs are key players in cardiac stress responses, but the mRNAs whose abundance and/or translational potential are primarily affected by changes in cardiac microRNAs are not well characterized. Stimulus-induced, large-scale alterations in the cardiac transcriptome, together with consideration of the law of mass action, further suggest that the mRNAs most substantively targeted by individual microRNAs vary between unstressed and stressed conditions. To test the hypothesis that microRNA target profiles differ in health and disease, we traced the fate of miR-133a and miR-378 targets in mouse hearts undergoing pressure-overload hypertrophy. Methods and Results: Ago2 immunoprecipitation with RNA-sequencing (RISC-sequencing) was used for unbiased definition of microRNA-dependent and -independent alterations occurring amongst ~13,000 mRNAs in response to transverse aortic constriction (TAC), in response to the microRNA overexpression needed to define miR-133a and miR-378 targets and to track their fate, and in response to the combined stimuli. Of 51 direct targets of miR-133a defined in unstressed hearts (fold-change ≥25%, FDR&lt;0.02), only 8 (16%) continued to be targeted by miR-133a during TAC, while for miR-378 direct targets, 17 of 28 (61%) targets were maintained during TAC. Similarly, only 9% (for miR-133a) and 58% (for miR-378) of hundreds of indirectly affected mRNAs underwent comparable regulation, demonstrating that the significant effect of TAC on microRNA direct target selection resulted in wider alterations of signaling function. Numerous microRNA-mediated regulatory events occurring exclusively during pressure overload revealed signaling networks likely responsive to the endogenous decreases in miR-133a and miR-378 during TAC. Conclusions: Pressure overload-mediated changes in overall cardiac RNA content alter microRNA targeting profiles, reinforcing the need to define microRNA targets in tissue-, cell- and status-specific contexts. Such considerations need to be taken into account for tailoring of therapeutic manipulation of microRNAs toward the most appropriate microRNAs active under defined stimuli.
Abstract P1-11-01: Depression and anxiety after adjuvant ovarian function suppression in premenopausal breast cancer patients
Authors: HW Yi, SJ Nam, SW Kim, JE Lee, SK Lee, SY Bae, S Park, H-J Paik, JM Ryu
Journal: Cancer Research (2016)

Abstract Purpose The results of the Suppression of Ovarian Function Trial (SOFT) and the Tamoxifen and Exemestane Trial (TEXT) showed that ovarian function suppression (OFS) in premenopausal early breast cancer patients improves disease control. However, mood swings after OFS is one of the chief complaints to make patients stop undergoing endocrine therapy. Studies about complications of OFS in breast cancer patients are not established well. We designed this randomized controlled trial to evaluate psychological functioning of patients after undergoing adjuvant OFS by goserelin. Patients and Methods We randomly assigned 64 premenopausal women with hormone receptor positive early breast cancer to the tamoxifen or tamoxifen plus goserelin group for a period of 1 year. Participants were screened for depression and generalized anxiety disorder using Hamilton Rating Scale for Depression (HAMD), Hamilton Rating Scale for Anxiety (HAM-A), Anxiety Sensitivity Index (ASI) and Albany panic and phobia questionnaire (APPQ) at baseline, 6 months and 12 months. Brain-derived Neurotrophic Factor (BDNF) levels were measured, as well. The results were analyzed by using a linear mixed model and a generalized linear mixed model. Results Thirty two patients were distributed in each group, equally. Linear mixed-mixed model analyses revealed that, compared with HAM-A scores of each group at baseline, HAM-A scores at 12 months showed increments (p=0.0078). Among HAM-A questions, Questions for intellectual, sensory and autonomic status were scored significantly high at 12 months (p=0.0018, p=0.0132, p=0.0006). Platelet BDNF levels reported a statistically significant rise at 12 months (p=0.0006). There was no significant time-by-study group effect in all scales. Conclusion Compared with the patients without OFS, patients with Goserelin showed no difference in anxiety or depression scales. Thought the levels of anxiety of each group at 12 months were increased, they do not indicate medical interventions. Patients with increased levels of BDNF at 12 months are expected to have good recovery from anxious and depressive symptoms. Citation Format: Yi HW, Nam SJ, Kim SW, Lee JE, Lee SK, Bae SY, Park S, Paik H-J, Ryu JM. Depression and anxiety after adjuvant ovarian function suppression in premenopausal breast cancer patients. [abstract]. In: Proceedings of the Thirty-Eighth Annual CTRC-AACR San Antonio Breast Cancer Symposium: 2015 Dec 8-12; San Antonio, TX. Philadelphia (PA): AACR; Cancer Res 2016;76(4 Suppl):Abstract nr P1-11-01.
Shouting<i>stat</i>in a crowded theater: the epidemic of pseudoemergencies
Authors: Saurabh Jha
Journal: BMJ (2015)

My love affair with stat started in medical school, when I learnt medicine on ward rounds and from Robbins Textbook of Pathology and the TV drama ER. 

Stat commanded but was not a commandment. Derived from statim , meaning immediate, stat recognized that the patient’s clinical course was doomed unless we intervened. It was Newton’s first law of motion, in motion.

“CBC, Chem 7, cross match, and six units of blood. Stat. ”

“Tension pneumothorax, he needs a chest tube. Stat. ”

Stat crystallized acute medicine—urgent, instinctive, and consequential. It raised us above the parapet. No gratitude was needed. Stat , please didn’t have the same ring to it. Stat …
BRIEF COMMUNICATION: Growth Control of Human Colon Cancer Cells by Vitamin D and Calcium In Vitro
Authors: H. S. Cross, M. Pavelka, J. Slavik, M. Peterlik
Journal: JNCI Journal of the National Cancer Institute (1992)

Journal Article BRIEF COMMUNICATION: Growth Control of Human Colon Cancer Cells by Vitamin D and Calcium In Vitro Get access Heide S. Cross, Heide S. Cross * Department of General and Experimental Pathology, University of Vienna Medical SchoolAustria *Correspondence to : Heide S. Cross, Ph.D., Department of General and Experimental Pathology, University of Vienna Medical School, Waehringer Guertel 18–20, A-1090 Vienna, Austria. Search for other works by this author on: Oxford Academic PubMed Google Scholar Margit Pavelka, Margit Pavelka Institute of Micromorphology and Electron Microscopy, University of Vienna Medical SchoolAustria Search for other works by this author on: Oxford Academic PubMed Google Scholar Jan Slavik, Jan Slavik Institute of Physiology, Czechoslovak Academy of SciencesPrague Search for other works by this author on: Oxford Academic PubMed Google Scholar Meinrad Peterlik Meinrad Peterlik Department of General and Experimental Pathology, University of Vienna Medical SchoolAustria Search for other works by this author on: Oxford Academic PubMed Google Scholar JNCI: Journal of the National Cancer Institute, Volume 84, Issue 17, 2 September 1992, Pages 1355–1357, https://doi.org/10.1093/jnci/84.17.1355 Published: 02 September 1992 Article history Received: 25 March 1992 Revision received: 15 June 1992 Accepted: 19 June 1992 Published: 02 September 1992