tbuckley/cabot-search huggingface dataset:
Abstract 5684: Target tubulin polymerization with novel reverse ABI analogs interacting with the colchicine binding site.
Authors: Min Xiao, Sunjoo Ahn, Jianjun Chen, Jin Wang, Duane D. Miller, James T. Dalton, Wei Li
Journal: Cancer Research (2013)

Abstract Cancer remains one of the leading causes of mortality worldwide. While current therapies are effective in treating early stage cancers, their efficacy against advanced cancers, especially multidrug-resistant cancers, is limited. Our lab recently reported a set of 2-aryl-4-benzoyl-imidazoles (ABI) derivatives with potent anti-proliferative activity against melanoma and prostate cancer cell lines and xenografts. Further optimization has led to the synthesis of a new series of 4-aryl-2-benzoyl-imidazoles with the aryl group and the benzoyl group reversed as compared to the previous ABI structure. The reverse ABI (RABI) compounds were evaluated for biological activity against 8 cancer cell lines including some which were multidrug-resistant. The in vitro results showed that several RABI compounds had excellent antiproliferative properties with IC50 values in the low namomolar range, comparable to existing tubulin-targeting agents such as paclitaxel, colchicine, or vinblastine, but with the ability to effectively circumvent Pgp-mediated drug resistance. The IC50 of the most active compound 12a was 9 nM. The mechanism of action (MOA) of the RABI compounds was investigated using cell cycle analysis, tubulin polymerization assays and molecular docking studies. These studies showed that their antitumor activity was achieved through inhibition of tubulin polymerization at the colchicine binding site. Our results suggest that the novel RABI compounds may be developed as a promising antitumor agent for advanced cancers. Citation Format: Min Xiao, Sunjoo Ahn, Jianjun Chen, Jin Wang, Duane D. Miller, James T. Dalton, Wei Li. Target tubulin polymerization with novel reverse ABI analogs interacting with the colchicine binding site. [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 5684. doi:10.1158/1538-7445.AM2013-5684
Comorbidity description using the hematopoietic cell transplantation-specific comorbidity index (HCT-CI) in elderly de novo poor-risk AML patients (pts) treated with laromustine
Authors: G. J. Schiller, S. M. O'Brien, N. Vey, A. Pigneux, D. J. DeAngelo, J. E. Karp, D. Hudak, J. Kell, R. K. Stuart, F. J. Giles
Journal: Journal of Clinical Oncology (2009)

7050 Background: Treatment of older pts with AML is often complicated by comorbidities and pts with comorbidities are often underrepresented in clinical trials. The HCT-CI, which was developed in pts receiving allogeneic SCT, has been applied to pts receiving induction therapy for AML in an effort to assist in therapeutic and investigational decisions (Kantarjian 2006; Etienne 2007; Giles 2007). HCT-CI scores have been shown to be predictive of early death and survival in pts ≥ 60 years receiving induction therapy for AML, with early death rates of 3%, 11%, and 29% for pts with HCT-CI scores of 0, 1–2, and ≥ 3, respectively (Giles 2007). Methods: 140 pts age ≥ 60 with poor risk de novo AML from two phase II studies were scored for comorbidity by HCT-CI. In these studies, poor risk was defined by the presence of at least one risk factor: age ≥ 70, ECOG PS = 2, unfavorable cytogenetics, or cardiac, pulmonary, or hepatic dysfunction. All pts received induction therapy with 600 mg/m 2 laromustine as a single 30–60 min infusion. A second induction cycle could be administered to pts with PR or hematologic improvement. Pts with CR or CRp were able to receive consolidation with laromustine 400 mg/m 2 (Study CLI-033) or araC 400 mg/m 2 /day CIV for 5 days (Study CLI-043). Results: HCT-CI score was 0 in 7 (5%) pts, 1–2 in 19 (14%), and ≥ 3 in 114 (81%). The median HCT-CI score was 5 (range 0–13). The most common comorbidities were cardiac (42%), severe pulmonary (39%), infection (35%), and arrhythmia (31%). 52 (37%) of all pts achieved a CR/CRp; 39/114 (34%) of pts with HCT-CI score ≥ 3 achieved a CR/CRp. Deaths within 30 days of first induction were observed in 0/7 pts with HCT-CI score 0, 4/19 (21%) with score 1–2, and 16/114 (14%) with score ≥ 3. Overall survival at 12 months was 43%, 14%, and 21% for pts with HCT-CI scores of 0, 1–2, and ≥ 3, respectively. Conclusions: The majority (81%) of these older poor risk AML pts treated with laromustine had a HCT-CI score ≥ 3, confirming the poor risk nature of this patient group. The induction death rate for pts treated with laromustine and with HCT-CI score ≥ 3 was lower than that reported for a group of pts with HCT-CI score ≥ 3 treated with standard induction chemotherapy (14% vs 29%; Giles 2007). [Table: see text]
Abstract 1342: Genetic variations in the MUC16 gene encoding tumor marker CA125 and their association with the risk of epithelial ovarian cancer.
Authors: Kristina Williams, Kathryn Terry, Allison Vitonis, Daniel Cramer
Journal: Cancer Research (2013)

Abstract Purpose: MUC16 is a cell surface mucin that is expressed at high levels by epithelial ovarian tumors, and is detected in serum as the CA125 antigen. MUC16 is clinically used as a tumor marker in the management of ovarian cancer and has been associated with prognosis. MUC16 is also thought to play an important role in ovarian tumor cell survival and metastasis. We studied the association of four tagging SNPs of the MUC16 gene (rs2547065 (C/G), rs1559168 (A/T), rs2121133 (A/G), rs2121133 (A/G)) and risk of ovarian cancer as well as the correlation of these SNPs with CA125 levels. Methods: MUC16 polymorphisms were genotyped using blood samples collected from 760 women diagnosed with ovarian cancer and 788 healthy controls enrolled in the New England Case-Control Study between 2003 and 2008. 388 cases had preoperative CA125 levels abstracted from medical records. Odds ratios and 95%CIs were calculated using logistic regression; polytomous (multinomial) logistic regression was used to estimate multivariate odds ratios by ovarian cancer histological subtype. The association between log normalized pre-operative CA125 levels and MUC 16 SNPs was evaluated using generalized linear models. Results: A significant association was observed between the rs2547065 polymorphism and ovarian cancer risk (per allele: OR=1.30, 95% CI: 1.11-1.52). The risk was greatest for women carrying two copies of the variant allele (OR=1.78, 95% CI: 1.29-2.45). When stratified by histological subtype, these associations were most apparent in the recessive model for women with serous invasive (OR = 1.69; 95%CI: 1.15-2.48) and clear cell (2.49 95% CI: 1.13-5.52) tumors. There were no significant associations between the other three MUC16 SNPs (rs1559168, rs2121133, rs12984471) and ovarian cancer risk. The rs2547065 polymorphism was not found to be associated with pre-operative CA125 levels in cases overall or in the subset of women with serous and clear cell cancers. Conclusions: These results suggest that women who carry one or more variant alleles of MUC16 SNP rs2547065 have an increased risk of ovarian cancer of the serous invasive and clear cell histological subtype. Further study of MUC 16 SNPs in relation to risk of ovarian cancer and their effect on CA125 levels is warranted. Citation Format: Kristina Williams, Kathryn Terry, Allison Vitonis, Daniel Cramer. Genetic variations in the MUC16 gene encoding tumor marker CA125 and their association with the risk of epithelial ovarian 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 1342. doi:10.1158/1538-7445.AM2013-1342
Complete Remission after Treatment of Acute Promyelocytic Leukemia with Arsenic Trioxide
Authors: Steven L. Soignet, Peter Maslak, Zhu-Gang Wang, Suresh Jhanwar, Elizabeth Calleja, Laura J. Dardashti, Diane Corso, Anthony DeBlasio, Janice Gabrilove, David A. Scheinberg, Pier Paolo Pandolfi, Raymond P. Warrell
Journal: New England Journal of Medicine (1998)

Two reports from China have suggested that arsenic trioxide can induce complete remissions in patients with acute promyelocytic leukemia (APL). We evaluated this drug in patients with APL in an attempt to elucidate its mechanism of action.
<i>Chlamydia trachomatis</i>as a Cause of Acute “Idiopathic” Epididymitis
Authors: Richard E. Berger, E. Russell Alexander, George D. Monda, Julian Ansell, Gerald McCormick, King K. Holmes
Journal: New England Journal of Medicine (1978)

To assess the etiologic role of C. trachomatis and other micro-organisms in "idiopathic" epididymitis, 23 men underwent microbiologic studies, including cultures of epididymal aspirates in 16. Eleven of 13 men under the age of 35 years had C. trachomatis infection whereas eight of 10 over 35 had coliform urinary-tract infection. Cultures of epididymal aspirates yielded C. trachomatis alone in five of six men under 35, and coliform bacteria alone in five of 10 over 35. These results suggest that C. trachomatis is the major cause of "idiopathic" epididymitis, and coliform bacteria the major cause of epididymitis in older men. Expressible urethral discharge and inguinal pain were more common in the chlamydial cases, whereas concurrent genitourinary abnormality and scrotal edema and erythema occurred more commonly in the coliform cases. The morbidity attributable to C. trachomatis is as serious as that attributable to Neisseria gonorrhoeae.To assess the etiologic role of C. trachomatis and other microorganisms in idiopathic epididymitis, 23 men underwent microbiologic studies, including cultures of epididymal aspirates in 16. 11 of 13 men under age 35 had C. trachomatis infection whereas 8 of 10 over age 35 had coliform urinary tract infection. Cultures of epididymal aspirates yielded C. trachomatis alone in 5 of 6 men under 35, and coliform bacteria alone in 5 of 10 over 35. These results suggests that C. trachomatis is the major cause of idiopathic epididymitis, and coliform bacteria the major cause of epididymitis in older men. Expressible urethral discharge and inguinal pain were more common in the chlamydial cases, whereas concurrent genitourinary abnormality and scrotal edema and erythema occurred more commonly in the coliform cases. The morbidity attributable to C. trachomatis is as serious as that attributable to Neisseria gonorrhoeae.
FRI0332 Evaluation of treatment in PFAPA syndrome: International cohort and literature review
Authors: A. Von Scheven-Gête, P. Pillet, P. Krol, I. Kone-Paut, D. Rigante, B. Bader-Meunier, V. Hengten, S. Berg, M. Gattorno, M. Hofer
Journal: Annals of the Rheumatic Diseases (2013)

<h3>Background</h3> PFAPA syndrome (periodic fever, aphtosis, pharyngitis and adenitis) is the most frequent cause of recurrent fever of inflammatory origin in pediatrics. Available treatments are designed to interrupt the episodes and others to prevent the recurrence of the febrile episodes (baseline treatment). <h3>Objectives</h3> Evaluation of the efficacy of the different treatments in our international cohort of PFAPA patients and comparison of these data with the results from the literature. <h3>Methods</h3> We extracted the information regarding the treatments of 301 PFAPA patients who were included between 2007 and 2009 in our database. The treatment response was evaluated as absent, incomplete or complete. Literature search was done by medline and English and French written publications were analyzed. <h3>Results</h3> Half of the patients were treated with corticosteroids which have an excellent efficacy to interrupt the febrile episodes with a response rate in 94%. NSAIDs and Paracetamol were taken in nearly 70% of patients with only a response rate (mainly incomplete) of 55% and 33% respectively. Only 30% (91 patients) underwent a baseline treatment. Among these treatments, adenotonsillectomy has the best response (90%) before tonsillectomy alone (68%). Colchicine, cimetidine and adenoidectomy alone were effective in only a minority of patients: cimetidine 25% (6/23), colchicine 33% (5/15), adenoidectomy 14% (1/7). In literature one retrospective study shows a response to colchicine with prolongation of fever free interval in 89%. Otherwise the literature contains only 2 randomized studies on PFAPA treatment; the other publications are non randomized trials, description of cohorts (15-105 patients) or case reports. The criteria used for selecting patients with PFAPA varied between the studies and are not always precisely mentioned. <h3>Conclusions</h3> In accordance with the literature, we show the efficacy of corticosteroids in treatment of febrile episodes and that adenotonsillectomy prevents febrile episodes in a significant number of patients. With regard to this cohort and the literature we recommend starting the treatment with corticosteroids. Colchicine can be added in association with the corticosteroids in PFAPA patients who have febrile episodes with short intervals and an important repercussion on every-day live. In children with failure of medical treatment and important repercussion of the quality of life, surgery should be considered. However the evidence showed in the publications on the efficacy of treatments in PFAPA lack strong evidences. The principal weaknesses are the absence of precise and validated diagnostic criteria and the low number of randomized studies. Our work underlines the necessity of controlled trials in large and homogenous cohorts of patients with PFAPA. <h3>Disclosure of Interest</h3> None Declared
Abstract 3317: Efficacy of <i>Salmonella typhimurium</i> A1-R treatment on human patient pancreatic tumorgrafts.
Authors: Ming Zhao, Matthew H.G. Katz, Jason B. Fleming, Atsushi Suetsugu, Yong Zhang, Ali Maawy, Takashi Chishima, Kuniya Tanaka, Michael Bouvet, Yukihiko Hiroshima, Itaru Endo, Robert M. Hoffman
Journal: Cancer Research (2013)

Abstract We have previously developed the genetically-modified Salmonella typhimurium A1-R (A1-R) strain that selectively targets tumors and demonstrated its efficacy for various types of cancer cell lines in nude mouse models. The aim of this study is to determine the efficacy A1-R treatment for human-patient pancreatic tumorgrafts. Pancreatic-cancer-patient tumor specimens were initially established subcutaneously in NOD/SCID mice immediately after surgery. The patient tumors were then harvested from NOD/SCID mice and passed orthotopically in transgenic nude mice, expressing fluorescent protein in order for the tumors to acquire fluorescent stroma for imaging. After confirmation of tumor growth by fluorescence imaging, the nude mice were treated in the following groups: (1) 5-fluorouracil (5FU) (10 mg/kg, ip); (2) cisplatin (CDDP) (10 mg/kg, ip); (3) gemcitabine (GEM) (150 mg/kg, ip); (4) A1-R (A1-R) (1.5x108 cfu/body, ip); and (5) PBS (vehicle/control) (ip). Control, 5FU, CDDP, GEM and A1-R injections were performed on a weekly basis from day-21 after tumor implantation for 4 weeks. Animals were sacrificed at 7 weeks, and tumors were harvested for analysis. Each treatment arm involved 5 tumor-bearing mice. No significant effects on body weight, morbidity, or severe toxicities were observed in any treatment arm. The tumor weight of each group was as follows: (1) 5FU, 0.044 ± 0.027g; (2) CDDP, 0.04 ± 0.032g; (3) GEM, 0.058 ± 0.051g; (4) A1-R, 0.106 ± 0.038g; and (5) PBS, 0.258 ± 0.209g. S. typhimurium A1-R treatment significantly reduced the tumor weight compared to control treatment (p = 0.011), as did the other treatments including 5FU (p = 0.005), CDDP (p = 0.004), and GEM (p = 0.001). S. typhimurium A1-R treatment was effective for human pancreatic tumorgrafts and could be a promising therapy for human pancreatic cancer. Citation Format: Ming Zhao, Matthew H.G. Katz, Jason B. Fleming, Atsushi Suetsugu, Yong Zhang, Ali Maawy, Takashi Chishima, Kuniya Tanaka, Michael Bouvet, Yukihiko Hiroshima, Itaru Endo, Robert M. Hoffman. Efficacy of Salmonella typhimurium A1-R treatment on human patient pancreatic tumorgrafts. [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 3317. doi:10.1158/1538-7445.AM2013-3317
EUS-FNA PULMONAR: UNA HERRAMIENTA PARA EL DIAGNÓSTICO HISTOPATOLÓGICO DE NEOPLASIAS PULMONARES DE LOCALIZACIÓN PARAMEDIASTINICA
Authors: V González-Carrera, J Ulla-Rocha, S Perez Cachafeiro, M Ruiz-Barcia, L Rivas Moral, J Turnes Vázquez
Journal: Endoscopy (2011)

Introducción: La EUS-FNA está consolidada como método mínimamente invasivo en el estudio del mediastino. Más recientemente la EUS-FNA ha permitido obtención de muestras de lesiones pulmonares.
SAFETY OF ORAL DOFETILIDE RELOADING COMPARED TO INITIAL LOADING FOR TREATMENT OF ATRIAL ARRHYTHMIAS
Authors: Jae Hyung Cho, JoEllyn Abraham, Roxanne Kyriakakis, Patrick Tchou, Mandeep Bhargava, Walid Saliba, Bruce Wilkoff, Mina Chung
Journal: Journal of the American College of Cardiology (2015)
PALLIATIVE STENTING FOR MALIGNANT GASTRO-DUODENAL OBSTRUCTION–A DISTRICT GENERAL HOSPITAL EXPERIENCE
Authors: M Trotter, R Balamurugan, K Dear, G Naylor, N Everitt, K Ravi
Journal: Gut (2013)

<h3>Introduction</h3> For 5 years we have run a combined endoscopic and radiological service to treat malignant gastric outlet obstruction with stenting. In an age of centralization of services for upper GI malignancies we have looked at our outcomes from this service. <h3>Aims/Background</h3> To assess the outcomes of palliative stenting for malignant gastro-duodenal obstruction against published data. <h3>Method</h3> All patients who underwent palliative stenting for malignant gastro-duodenal tumours in our centre from 2007 up to January 2013 were retrospectively analyzed. Two patients were excluded due to non-availability of notes. Outcomes were assessed for technical and clinical success, return to oral nutrition, complication and re-intervention rates and overall survival. <h3>Results</h3> 32 stents were placed in 29 patients. The service was provided by the same radiologist in 94% of cases and by the same two endoscopists in 79% of cases. Technical success was 100% and clinical success and return to oral nutrition was 91%. Complication rate was 16% (2 stents migrations, one tumour overgrowth and two patients had food bolus obstruction). Re-intervention rate was 13% with 3 re-stenting procedures and 1 gastroenterostomy. Mean survival was 91 days (5–392). Median wait from decision to stent to actual stenting was 1 day, (0–14). Overall 25 covered and 9 uncovered stents were inserted. <h3>Conclusion</h3> Stenting for gastric outlet obstruction in this patient group is an established preferable alternative to surgical intervention. Much of the treatment for upper GI malignancies have now been centralized. Our data shows comparable results with other published data for these procedures with a high success rate and low major complication rates. It is of considerable benefit to these patients not to have to travel to a regional centre for stenting.
Doctors fail to get life support withdrawn from "minimally conscious" patient
Authors: O. Dyer
Journal: BMJ (2013)

The Supreme Court of Canada has dismissed an appeal by Toronto doctors who sought to withdraw life support from a severely brain damaged patient against his family’s wishes.

Hassan Rasouli, 61, has been kept alive on a ventilator and feeding tube since contracting meningitis after brain surgery at Toronto’s Sunnybrook Hospital in 2010. His wife, Parichehr Salasel, herself a physician in her native Iran, refused consent to end life support when his doctors concluded that further treatment offered no hope of recovery. She cited the couple’s …
COMPARISON OF THE CORONARY ARTERY CALCIUM SCORE FOR PREDICTING ALL-CAUSE MORTALITY IN AN ASIAN AND NON-ASIAN COHORT
Authors: Donghee Han, Briain O. Hartaigh, Ji Hyun Lee, Heidi Gransar, Hyo Eun Park, Su-Yeon Choi, Jidong Sung, Tracy Callister, James Min, Hyuk-Jae Chang
Journal: Journal of the American College of Cardiology (2016)
Pharyngeal webs in a patient with dysphagia and Behcet's disease
Authors: M. Efthymiou, S. Raftopoulos, P. Kortan
Journal: Endoscopy (2012)

A 64-year-old woman presented with longstanding dysphagia to solids and a recent onset of nocturnal cough and change in her voice. The patient described restriction to the passage of solids at the level of the neck, but denied odynophagia or weight loss. She had a background of Behcet's disease with previous colonic and oropharyngeal involvement. She had also been treated for many years with esophageal dilations for an upper esophageal web. Her symptoms of dysphagia improved temporarily after each dilation; however, typically there was recurrence within 2 weeks of treatment. Video fluoroscopy was performed, which demonstrated a small web in the region of the pharyngo-esophageal junction, above which there was pharyngeal dilatation. At least one episode of aspiration occurred during this procedure.
P694 HEPATITIS E INFECTION IN PATIENTS WITH SEVERE ACUTE ALCOHOLIC HEPATITIS
Authors: S. Haim-Boukobza, A. Coilly, M. Bouamoud, T.M. Antonini, M. Sebagh, O. Yordanova, J.-C. Duclos-Vallée, J. Savary, F. Saliba, D. Samuel, P. Ichai, A.-M. Roque-Afonso
Journal: Journal of Hepatology (2014)
P238 Competence in, and Safety of, Oxygen Prescribing by Medical Students Taking Final MBBS as Assessed by Objective Structured Clinical Examination
Authors: D Hammersley, A Connor, C Ward, S Kennedy, A Sturrock, LJ Restrick
Journal: Thorax (2012)

<h3>Introduction and Objectives</h3> National audits show oxygen prescribing is still not consistently safe and appropriate, despite the 2008 BTS Emergency Oxygen Guidelines. The aim of this study was to assess whether medical students taking Final MBBS examinations are able to prescribe oxygen safely and appropriately. <h3>Methods</h3> A 2012 medical school Final MBBS Objective Structured Clinical Examination station assessed oxygen prescribing. Candidates were presented with one of two clinical scenarios requiring an oxygen prescription on a drug chart; Scenario 1: 72-year-old patient with COPD, and Scenario 2: 72-year-old hypoxic patient without respiratory disease. Prescriptions from 227 out of 363 students taking MBBS were retrospectively assessed against BTS standards using the criteria; correct target saturation range, oxygen flow, device and frequency of delivery. The remaining prescriptions were not available for analysis. Prescriptions were classified as ‘safe/unsafe’ and ‘perfect (met all standards)/imperfect’ by a respiratory nurse specialist. <h3>Results</h3> 66/122 (54%) of candidates wrote the correct saturation range for the COPD scenario, compared with 42/105 (40%) for scenario 2. Oxygen flows were correct in 74/122 (60.6%) of COPD and 4/105 (3.8%) of scenario 2 prescriptions. The flow was appropriate for the device in 91.2% (207/227) and prescriptions specified ‘continuous’ oxygen in 60.8% (138/227). 59/122 (48.4%) prescriptions for COPD were safe and 26/122 (21.3%) ‘perfect’ compared with 19/105 (18.1%) safe and 0/105 (0%) perfect prescriptions for the hypoxic patient without respiratory disease. 185/363 (51%) students passed this station with overall year pass rate for finals 96% (349/363). <h3>Conclusions</h3> This study demonstrates an important unmet need in undergraduate education as competence in, and safety of, oxygen prescribing by otherwise successful MBBS candidates was poor. Of the prescriptions available for analysis, only half used appropriate target saturations. Half of prescriptions for COPD scenario were safe but only one in five met all BTS standards. No prescriptions for hypoxia without respiratory disease met all standards and one in five was safe. We believe that this reflects the undergraduate teaching focus on oxygen in COPD. We recommend introducing a compulsory undergraduate e-learning module on oxygen delivery and prescribing as newly-qualified doctors need to be able to prescribe oxygen safely.