tbuckley/cabot-search huggingface dataset:
Abstract 2854: Delineation of grade-specific molecular drivers in inducible preclinical mouse models of astrocytoma
Authors: Yurong Song, Qian Zhang, Ryan Bash, Chaoying Yin, Chunyu Yang, Debra Gilbert, Sophie Wang, Elizabeth Bullitt, Tal Kafri, Ken D. McCarthy, David N. Louis, C. Ryan Miller, Terry Van Dyke
Journal: Cancer Research (2011)

Abstract Glioblastoma (GBM) is a uniformly lethal neoplasm that accounts for 20% of all primary brain tumors. Despite advances in multimodality therapy, the median survival for patients with this disease remains approximately 12 months and has changed little over the past 40 years. An increased understanding of the molecular genetic basis of gliomagenesis is urgently required to develop more effective therapies for this devastating disease. Recently, The Cancer Genome Atlas (TCGA) project reported the most extensive genetic analysis of GBMs enhancing our ability to query altered signaling pathways potentially involved. Yet, an understanding of disease etiology requires extensive modeling in mammalian genetic systems coupled with analyses of biological contributions of disease. Here we genetically perturbed the primary molecular pathways (pRb and Ras) in genetically engineered mouse models (GEM). Alterations were induced specifically in adult GEM astrocytes via a tamoxifen-inducible, human GFAP promoter-driven CreERTM allele. GEM with astrocyte RB pathway inactivation alone (T) developed low-grade astrocytomas (grade II). Constitutive KRAS activation alone (R) did not produce detectable brain pathology. GEM harboring both inactivated RB and constitutively active KRAS (TR) in astrocytes developed high-grade astrocytomas (grade III) with low frequency of GBM development (grade IV). Deletion of Pten further progressed the tumor to grade IV with high frequency. Mechanistically, pRb inactivation led to activation of MAPK pathway via Ras. Mutant Kras did not further activate MAPK. Instead, it activated PI3K pathway. Deletion of Pten further activated PI3K-AKT pathway, leading to higher GBM rate. These highly penetrant, inducible GEM models provide a unique system for delineating the downstream pathways and resulting biological abnormalities critical to astrocytoma pathogenesis and for preclinical drug and biomarker development. Initial studies have begun to define the relative contribution to disease of each disrupted pathway, including potential targets for therapeutic intervention. Citation Format: {Authors}. {Abstract title} [abstract]. In: Proceedings of the 102nd Annual Meeting of the American Association for Cancer Research; 2011 Apr 2-6; Orlando, FL. Philadelphia (PA): AACR; Cancer Res 2011;71(8 Suppl):Abstract nr 2854. doi:10.1158/1538-7445.AM2011-2854
FDG PET/CT in Sarcomatoid Carcinoma of the Gallbladder With Chondroid Differentiation
Authors: Aisheng Dong, Hui Dong, Wei Jing, Changjing Zuo
Journal: Clinical Nuclear Medicine (2016)

Sarcomatoid carcinoma of the gallbladder, composed of epithelial and sarcomatous components, is a rare malignant tumor with a poor prognosis. A 61-year-old man was admitted because of abdominal distention for 2 weeks. Enhanced CT showed a large gallbladder tumor with central necrosis. The tumor measuring 18 cm in maximum diameter showed intense peripheral FDG uptake with SUVmax of 15.4. The specimen of the resected tumor revealed tubular adenocarcinoma and sarcomatoid tissue with chondroid differentiation. Immunohistochemical staining showed the sarcomatoid tissue was positive for EMA, CD10, and VIM, with proliferation index of 80%. These pathologic findings were consistent with sarcomatoid carcinoma.
Evaluation of Surgical Completeness in Endoscopic Thyroidectomy Compared With Open Thyroidectomy With Regard to Remnant Ablation
Authors: Hyung-Jun Im, Do Hoon Koo, Jin Chul Paeng, Kyu Eun Lee, Yoo Seung Chung, Ilhan Lim, Dong-Soo Lee, June-Key Chung, Yeo-Kyu Youn
Journal: Clinical Nuclear Medicine (2012)

Purpose: To assure the surgical completeness of the bilateral axillo-breast approach (BABA) endoscopic thyroidectomy (ET), we compared ET and open thyroidectomy (OT) by means of the radioactive iodine (RAI) uptake of remnant thyroid. Materials and Methods: From January 2003 to May 2007, 46 patients who had received RAI ablation after total thyroidectomy because of papillary thyroid microcarcinoma were enrolled. Of total, 25 patients underwent ET and the other 21 underwent OT. The RAI activity of remnant thyroid was measured by the neck-to-skull uptake ratio on the first postoperative RAI ablation scan. Stimulated thyroglobulin levels, the total number of RAI ablation sessions, and doses of RAI for completion of ablation were also compared. Results: There were no significant differences in regards of the RAI uptake ratio, the stimulated thyroglobulin level, the total number of RAI ablation sessions, and doses of RAI for completion of ablation, between ET and OT groups. Conclusion: The completeness of the surgical removal by BABA ET was comparable with that of OT. The BABA ET might give a safe option for patients with low-risk thyroid cancer.
FRI0172 The perioperative use of anti-tnf therapies in patients with rheumatoid arthritis undergoing elective orthopaedic surgery: a survey of current practice
Authors: M. A. Lee, M. Perry, J. Keenan
Journal: Annals of the Rheumatic Diseases (2013)

<h3>Background</h3> An increasing number of patients with RA are now being managed with anti-TNF therapies. However, there appears to be some confusion amongst health care professionals working in both Rheumatology and Orthopaedics as to when these therapies should be discontinued prior to elective orthopaedic surgery. There is conflicting data in the current literature with regards to perioperative infection and anti-TNF use. The BSR recommendations sate that "if anti-TNF treatment is to be stopped prior to surgery, consideration should be given to stopping at a time 3 to 5 times the half-life for the relevant drug before surgery (infliximab 8-9.5 days, etanercept 100 hours, adalimumab 15-19 days)"[1]. There is some confusion as to whether the figures stated in the recommendations refer to the half-lives of the drugs themselves or the time the guidelines recommend stopping the drugs prior to surgery. <h3>Objectives</h3> We conducted an e-mail survey of local practitioners to gain an understanding of current practice and whether that practice was in line with current national guidelines. <h3>Methods</h3> An e-mail survey of 131 consultant rheumatologists, rheumatology specialty trainees and rheumatology specialist nurses working in South-West England and Wales was conducted. Health care professionals were asked when they routinely stop infliximab, etanercept and adalimumab prior to routine elective orthopaedic surgery. <h3>Results</h3> 61 (47%) of health care professionals responded to the survey question, "How long prior to elective orthopaedic surgery do you routinely recommend stopping Infliximab, Etanercept and Adalimumab?" <h3>Conclusions</h3> In South-West England and Wales, the period prior to elective orthopaedic surgery that infliximab and etanercept are stopped is in keeping with BSR recommendations. However, the period between when adalimumab is stopped and when elective orthopaedic surgery occurs appears to be shorter than BSR recommendations. One potential reason for this discrepancy is the perception that adalimumab's half-life may be shorter than 15-19 days as injections are given more frequently than one may expect when the pharmacological half-life is taken into account. It may also be that rheumatologist stop adalimumab in a way that they believe is manageable for the patient's arthritis. <h3>References</h3> Ding T, Ledingham J, Luqmani R et al. BSR and BHPR rheumatoid arthritis guidelines on safety of anti-TNF therapies. Rheumatol 2010;49(11):2217-9 <h3>Disclosure of Interest</h3> None Declared
PWE-099 Contribution of surgery and disease subtype to health related quality of life in patients with locally advanced and recurrent colorectal cancer
Authors: P G Vaughan-Shaw, R Sreekumar, N J Curtis, M D Bullock, T Armstrong, A Bateman, T Bryant, J S Knight, M C Hayes, R W Lockyer, M Phillips, A H Mirnezami
Journal: Gut (2012)

<h3>Introduction</h3> Management of patients with locally advanced (LA) and locally recurrent (LR) colorectal cancer is challenging, with patients frequently requiring complex multimodality interventions. Despite increasing emphasis on evaluation of health related quality of life (HRQoL) in patients having complex interventions, HRQoL information on patients with LA and LR colorectal cancer is sparse. The aim of this study was to prospectively assess outcome measures and HRQoL in a cohort of patients with LA and LR colorectal cancer at our institution. <h3>Methods</h3> LA disease was defined as tumour requiring extended multi-visceral resection in the abdomen or pelvis to achieve an R0 resection. 45 consecutive patients were prospectively assessed over a 2-year period. Demographic, treatment, and cancer-related outcomes were recorded on all patients. Pelvic disease was staged using Leeds and Royal Marsden Hospital classification systems. HRQoL was prospectively evaluated using the EORTC generic and disease specific instruments QLQ-CR30 and QLQ-CR29. <h3>Results</h3> Median age was 69 (range 46–89) and 60% were male (27/45). There were 25 cases of LA disease and 20 LR cases. 35 patients underwent surgery while 10 patients had non-surgical palliation. R0 resection rate was 94%. HRQoL data were available on 41 patients. Median global health status was 65 (95% CI 55.5 to 74.1), physical functioning 77 (95% CI 69.9 to 84.5), and social functioning 72 (95% CI 60.3 to 83.8), which compared favourably with published EORTC reference values. Global health status and pain were significantly better in patients having surgery compared to non-surgical palliation (p&lt;0.0001 and p&lt;0.0004). Assessment of individual function and symptom scales revealed no significant difference in HRQoL between LA and LR except for greater buttock pain in patients with LR disease. <h3>Conclusion</h3> In carefully selected patients, HRQoL after radical multimodality treatment for LA and LR colorectal cancer is acceptable, and gives better results than palliation. <h3>Competing interests</h3> None declared.
SPECT/CT Unequivocally Depicts Dilated Cystic Duct Sign on Hepatobiliary Scintigraphy in Acute Cholecystitis
Authors: Mark Tulchinsky
Journal: Clinical Nuclear Medicine (2013)

The dilated cystic duct sign (DCDS) on hepatobiliary scintigraphy can lead to a false-negative test in patients with acute cholecystitis. Presented is a case of acute gangrenous cholecystitis with probable DCDS on the planar study that was unequivocally delineated on SPECT/CT imaging. SPECT/CT may be useful when planar findings suggest DCDS.
Butterfly Lesion of the Corpus Callosum
Authors: Pin Lin Kei, Tian Yue Kok, Yeh Ching Linn, Ajit K. Padhy
Journal: Clinical Nuclear Medicine (2011)

A 49-year-old male patient presented with worsening forgetfulness for 2 months, without any focal neurologic signs. CT and MRI scans showed a small enhancing mass in the right frontal periventricular region and another larger characteristic "Butterfly" lesion within the splenium of the corpus callosum. Provisional diagnosis of lymphoma or glioblastoma multiforme was made. F-18 FDG PET/CT scan showed hypermetabolism of these lesions. The final histology revealed leukocytic large-cell neoplasm, compatible with extramedullary myeloid sarcoma (or granulocytic sarcoma). This case shows an unusual manifestation of myeloid sarcoma presenting as a lesion in the corpus callosum.
Soundings: Be very afraid
Authors: Liam Farrell
Journal: BMJ (2000)

“Beware the Jabberwock, my son,

The jaws that bite, the claws that catch . . .”

Danger can be obvious, something dark and wicked, easy to perceive and to shun. But, as any heartbroken lover will tell you, when it comes in the guise of something beautiful, something gentle and kind, it is hard to recognise and avoid, and then it is perilous indeed.

Two of my patients died last week. I'd looked after them for years, and they were good people and easy to be good to, but I can't pretend to have felt any great grief over their deaths. Over the years I've got pretty hardy, not one to blubber.

We are not made of rock, but of flesh and blood; we are not gods, just simple men and women doing our best. You can care deeply for your patients, like them, be their friend as well as their doctor, and that's as it should be, but there is a thin line to be crossed where we give too much of ourselves.

“Equanimity,” according to William Osler, was what we should strive for, and most of us do manage to muddle through somehow.

No matter how exquisite the pain, we usually walk away after our shift and forget about it, watching a game of football, having dinner with our family, a few beers with friends. We go back to our own lives. Yea, tho we walk in the Valley of the Shadow of Death, once I'm out of the Valley it's not my problem anymore.

But we do have to care a little bit, and sometimes our profession can let us down very badly. A tribunal is under way in the Republic of Ireland at present to investigate the use of contaminated blood products which led to many people with haemophilia developing AIDS and hepatitis C, the cure devastatingly worse than the disease; don't trust me, I'm a doctor.

Whether this was a result of incompetence or laziness or bad luck or lack of resources is not yet clear. We have only heard the patients' side of the story, and no matter how stark the tragedy it is too simplistic to look for scapegoats; doctors are easy targets for blame.

But what has clearly emerged is a picture of an aloof, secretive, and unfeeling profession. Even after the mistake was made some of these patients were treated with an offhand discourtesy that seems barely credible.

Surely this picture can't be right; surely.
P490 URINARY METABOLIC PROFILING BY H NMR SPECTROSCOPY IN PATIENTS WITH CIRRHOSIS DISCRIMINATES OVERT BUT NOT MINIMAL HEPATIC ENCEPHALOPATHY
Authors: M.J. McPhail, M. Villa, I.J. Cox, R. Williams, P. Amodio, S. Montagnese, S.D. Taylor-Robinson
Journal: Journal of Hepatology (2014)
Facilitating Transthoracic Cardioversion of Atrial Fibrillation with Ibutilide Pretreatment
Authors: Hakan Oral, Joseph J. Souza, Gregory F. Michaud, Bradley P. Knight, Rajiva Goyal, S. Adam Strickberger, Fred Morady
Journal: New England Journal of Medicine (1999)

Atrial fibrillation cannot always be converted to sinus rhythm by transthoracic electrical cardioversion. We examined the effect of ibutilide, a class III antiarrhythmic agent, on the energy requirement for atrial defibrillation and assessed the value of this agent in facilitating cardioversion in patients with atrial fibrillation that is resistant to conventional transthoracic cardioversion.
FRI0237 Study of the antibody titer by influenza vaccination in rheumatoid arthritis patients treated with biological agents
Authors: H. Ishikawa, H. Kanda, D. Kida, A. Kaneko, M. Katayama, T. Sato
Journal: Annals of the Rheumatic Diseases (2013)

<h3>Background</h3> Biologic agents might suppress the immune response to influenza vaccines, but, the report is limited to the number of papers. <h3>Objectives</h3> The aim is the study to compare antibody titers change after influenza vaccination for rheumatoid arthritis (RA) patients who have been treat with methotrexate (MTX ;contorol), abatacept (ABT), tocilizumab (TCZ), golimumab (GLM). <h3>Methods</h3> 189 patients with RA (MTX;n=56, ABT;n=37, TCZ;n=79, and GLM;n=17) received inactive trivalent influenza vaccination (A/H1N1, A/H3N2, B/B-1 strains). Antibody titer were measured before and one month after vaccination using the haemagglutination inhibitory assay. <h3>Results</h3> Compared with the control, Biologic agents, but only showed a difference of type B in seroprotection rate, there was no difference in the seroconversion rate (table 1). In seroconversion rates tended to be lower in all strains ABT. It was a significant difference in all strains to TCZ. No difference was observed in the control and GLM. In seroprotection rate, ABT was still lower value. It was a significant difference in the same manner in all strains to TCZ, Only A/H3N2, the control difference was observed, there was no difference in the GLM (table 2). <h3>Image/graph</h3> <h3>Conclusions</h3> In our result, There was little difference between the control and Biologics (ABT, TCZ, GLM). The patients treated with ABT, antibody titers were low, and was a significant difference of both seroprotection rate and seroconversion rate to TCZ. The patients thought that the examination of the multiple dose etc. of the vaccine was necessary in the future. <h3>References</h3> <h3>Acknowledgements</h3> <b>Disclosure of Interest</b>: None Declared
AB1133 Comparison of Canadian and Israeli Rheumatologists' Understanding of Cannabinoid Use as A Therapy for Rheumatic Diseases
Authors: M.-A. Fitzcharles, P.A. Ste-Marie, J.N. Ablin, Y. Shir
Journal: Annals of the Rheumatic Diseases (2014)

<h3>Background</h3> Canada and Israel are at the forefront in legalizing herbal cannabis for therapeutic reasons. Musculoskeletal complaints are a common reason for persons using medical cannabis, with nearly two thirds of current Canadian authorizations to use cannabis medically carrying a diagnosis "severe pain" caused by "severe arthritis" [1]. <h3>Objectives</h3> As rheumatologists are specialised in caring for patients presenting with musculoskeletal complaints, the confidence of rheumatologists9 knowledge of cannabinoids was compared in the two countries. <h3>Methods</h3> All members of the Rheumatology Associations of Canada and Israel were surveyed by e-mail for their confidence in knowledge of cannabinoids and their perceived competence to prescribe herbal cannabis. <h3>Results</h3> The response rate for Canada and Israel was 25% and 20% respectively. Demographics of the responders from both countries was similar for gender, age, and years in practice, but with more Israeli responders in community/private practice, p&lt;0.0001. Three quarters of responders in both countries were not confident about their knowledge of cannabinoid molecules or ability to write a prescription for herbal cannabis. Differences between country responses for Canada vs. Israel were as follows: no role for any cannabinoid treatments, 45 vs 17%, p=0.019, never previously recommended trial any cannabinoid, 70 vs 39%, p=0.0075, some role for pharmacologic or herbal preparations, 30 vs. 48%, p=0.096, willing to prescribe herbal cannabis if other treatments failed, 28 vs 83% p&lt;0.0001. The majority of respondents were not confident to write a prescription for herbal cannabis, 90 vs 78%, p=0.154. <h3>Conclusions</h3> Although rheumatologists in both countries lack confidence in their knowledge of cannabinoids in general, Israeli rheumatologists were more open to cannabinoid treatments, with more willingness to prescribe, although the majority lacks confidence in prescribing the herbal product. <h3>References</h3> Office of the Information Commissioner of Canada, Information request (ATI 2013-00282) under the Access to Information Act, 2013. <h3>Disclosure of Interest</h3> M.-A. Fitzcharles Speakers bureau: Lilly, Pfizer, Purdue, Valeant, P. Ste-Marie: None declared, J. Ablin Consultant for: Pfizer, Lilly, MSD, Y. Shir Consultant for: McKesson Canada Corporation, Palladin Inc. Canada <h3>DOI</h3> 10.1136/annrheumdis-2014-eular.2511
Abstract 4949: Combined immunochemotherapy for poor prognosis breast cancer.
Authors: Anna Wasiuk, Hope Rugo, Lisa M. Coussens
Journal: Cancer Research (2013)

Abstract Using preclinical mouse models of luminal B-type mammary adenocarcinoma (e.g., MMTV-PyMT mice), we, and others have reported that immune microenvironments of mammary tumors can be therapeutically manipulated to enhance responses to chemotherapy (CTX)(1). To determine the degree to which other subtypes of mammary carcinoma are similarly susceptible to immune reprogramming, we evaluated transgenic models of basal-like/triple negative (TN), e.g., C3(1)-Tag (2), and erbB2-amplified, e.g., Erbb2f/f/MMTV-Cre (3), mammary adenocarcinoma, with clinical/preclinical agents acting to either deplete or re-educate tumor-associated macrophages, in combination with taxol-based CTX, e.g., paclitaxel, nab-paclitaxel or eribulin mesylate. Our preliminary studies reveal similar complexity of immune cells infiltrating basal-like/TN tumors as what we previously reported for luminal B-type tumors where macrophages, as opposed to monocytes, are the predominate myeloid cells present. Significantly, mammary tumors in C3(1)-TAg mice exhibit improved responses to taxol-based CTX when given in combination with either colony stimulating factor-1 (CSF1) or CSF1 receptor (CSF1R) antagonists, as compared to either therapy alone, with no evident liver (ALT, AST, ALP) or kidney (Cre, BUN, CPK) toxicity. These studies reveal a synergistic benefit of combination macrophage-targeting immunotherapy with standard-of-care CTX regardless of mammary tumor subtype or form of taxol-based CTX. Thus, macrophage-targeting immunotherapy remains as an encouraging new neo-adjuvant strategy for slowing primary tumors and minimizing early metastasis. It remains to be determined if similar results will be realized with this class of agents in the metastatic setting. 1. DeNardo D, et al. Cancer Discov 1, 54-67 (2011) 2. Maroulakou I, et al., PNAS 91, 11236-11240 (1994) 3. Andrechek E, et al. PNAS 97, 3444-3449 (2000) Support provided from the NCI/NIH (R01CA15531), the DoD (W81XWH-11-1-0702) and the Susan G Komen Foundation (KG110560, KG111084). Citation Format: Anna Wasiuk, Hope Rugo, Lisa M. Coussens. Combined immunochemotherapy for poor prognosis breast cancer. [abstract]. In: Proceedings of the 104th Annual Meeting of the American Association for Cancer Research; 2013 Apr 6-10; Washington, DC. Philadelphia (PA): AACR; Cancer Res 2013;73(8 Suppl):Abstract nr 4949. doi:10.1158/1538-7445.AM2013-4949