tbuckley/cabot-search huggingface dataset:
PTH-038 Diagnostic utility of further assessment with endoscopic ultrasound in patients with unexplained common bile duct obstruction with and without abnormal liver enzymes: Abstract PTH-038 Table 1
Authors: W On, Y Lim, O Patani, N Kapoor
Journal: Gut (2015)

<h3>Introduction</h3> Patients who undergo endoscopic ultrasound (EUS) are often referred because of a dilated common bile duct (CBD) of unknown cause and/or abnormal liver enzymes (LFT). We aimed to determine the diagnostic yield when such patients are referred for an EUS for further assessment. <h3>Method</h3> All patients who underwent an EUS in 2010 were included. Patients who had an identifiable cause of pathology on prior imaging were excluded. We retrospectively analysed our electronic database for radiological evidence of CBD dilatation, laboratory values of LFT and results of the EUS. <h3>Results</h3> 184 patients were identified. 60 (32.6%) had a dilated CBD with normal LFT (group A), 65 (35.3%) had dilated CBD with abnormal LFT (group B), 36 (19.6%) had abnormal LFT with a normal CBD (group C), and 23 (12.5%) had normal LFT with a normal CBD (group D). Out of 184 patients, 78 (42.4%) received a diagnosis at EUS. The diagnostic yield of EUS when divided into groups were: A = 23.3% (14/60), B = 55.4% (36/65), C = 55.6% (20/36), D = 34.8% (8/23). There was a significant difference in diagnostic yield between groups A vs B and A vs C (p = &lt;0.05). When comparing patients with abnormal LFT (B+C) against patients with normal LFT (A+D), there was also a significant difference (p = &lt;0.05). <h3>Conclusion</h3> Patients with abnormal LFT were more likely to have a positive diagnosis at EUS than those with a dilated CBD. However there were substantive positive findings in all groups justifying further assessment with EUS even if prior imaging tests were normal. <h3>Disclosure of interest</h3> None Declared.
Evaluation of Circulating Tumour DNA for the Mutational Characterisation of Multiple Myeloma
Authors: Andrew Spencer, Sridurga Mithraprabhu, Malarmathy Ramachandran, Daniela Klarica, Jay Hocking, Laura Mai, Stephanie Walsh, David Broemeling, Andre Marziali, Anna Kalff, Matthew Wiggin, Brian G. M. Durie, Tiffany T. Khong
Journal: Blood (2015)
Biosimilars for psoriasis: clinical studies to determine similarity
Authors: A. Blauvelt, L. Puig, S. Chimenti, R. Vender, M. Rajagopalan, R. Romiti, L. Skov, C. Zachariae, H. Young, E. Prens, A. Cohen, J. van der Walt, J.J. Wu
Journal: British Journal of Dermatology (2016)

Biosimilars are drugs that are similar, but not identical, to originator biologics. Preclinical analytical studies are required to show similarity on a molecular and structural level, but efficacy and safety studies in humans are essential to determining biosimilarity. In this review, written by members of the International Psoriasis Council, we discuss how biosimilars are evaluated in a clinical setting, with emphasis on extrapolation of indication, interchangeability and optimal clinical trial design.
Effective Ex Vivo-Generation and Quantification of Leukemia-Derived DC Has To Precede a Specific T-Cell Stimulation for Adoptive Immunotherapy in AML and MDS.
Authors: Helga Maria Schmetzer, Andreas Kremser, Julia Loibl, Nina Hentschel, Karin Steiner, Christoph Schmid, Tanja Kroell, Stefanie Kufner, Helmut Salih, Francesco del Valle, Constanze Doehner, Claudia Schweiger, Christian Schwartz, Wolfgang Hiddemann, Hans-Jochen Kolb
Journal: Blood (2005)
MiR-153/Kv7.4: a novel molecular axis in the regulation of hypertension
Authors: Angelo Maffei, Vittoria Di Mauro, Daniele Catalucci, Guiseppe Lembo
Journal: Cardiovascular Research (2016)

This editorial refers to ‘MicroRNA-153 targeting of KCNQ4 contributes to vascular dysfunction in hypertension’, by G. Carr et al. , pp. 581–589 

Characterized by a steady increase in blood pressure values, hypertension is a complex, multifactorial disease resulting from a combination of environmental and genetic factors. Blood pressure is a function of peripheral resistance, which in turn depends on arterial diameter. Several molecular mechanisms have been described as regulators of arterial diameter both chronically, leading to vascular remodelling, and acutely, by contraction or relaxation of vascular smooth muscle in the vessel wall. Although decades of research proposed several advances in anti-hypertensive therapies, there are still patients with uncontrolled hypertension, thus pressing the search for novel mechanisms underlying hypertension and its related cardiovascular modifications.

MicroRNAs, small non-coding RNAs that target messenger RNAs at the post-transcriptional level, are involved in virtually all biological processes, including cellular proliferation, apoptosis, and differentiation.1 Deregulation of many individual microRNAs has been linked to the development and progression of cardiovascular diseases, …
Use of EGF a+61G and TS-5'UTR 2R/3R polymorphisms to predict complete pathologic response in locally advanced rectal cancer patients undergoing preoperative cetuximab-based chemoradiation followed by surgery.
Authors: S. Hu-Lieskovan, D. Yang, P. P. Grimminger, D. Arnold, K. Dellas, J. H. Machiels, C. Roedel, V. Velenik, H. Lenz, D. Vallbohmer
Journal: Journal of Clinical Oncology (2010)

3641 Background: Cetuximab has demonstrated significant clinical activity in metastatic colon cancer, however, cetuximab-containing neoajuvant chemoradiation has not been shown to improve local control or survival in locally advanced rectal cancer patients based upon recent phase II trials. In order to identify the subgroup of patients who may benefit from the cetuximab protocol, we evaluated functional germline polymorphisms of genes involved in critical pathways of cancer progression i.e., tumor growth (COX-2, EGF, EGFR, Kras), cell cycle regulation (CyclinD1), angiogenesis (VEGF, IL-8), ADCC (FCGR2A/3A), DNA repair (XRCC3, Rad51), and drug metabolism (TS, MTHFR), for their potential role as molecular predictors for clinical outcome in locally advanced rectal cancer patients treated with preoperative cetuximab-based chemoradiation followed by surgery. Methods: 130 patients (74 men and 56 women) with locally advanced rectal cancer (4 with stage II, 109 with stage III and 15 with stage IV, 2 unknown) who were enrolled in phase II clinical trials treated with cetuximab-based chemoradiation in European cancer centers were included. Genomic DNA was extracted from formalin-fixed paraffin-embedded tumor samples and genotyping was performed using PCR-RFLP assays. Fisher's exact test was used to examine associations between polymorphisms and complete pathologic response (pCR) that was determined by a modified Dworak classification system (grade 0-III vs grade IV: complete response). Results: Germline polymorphisms of EGF and TS were predictive for histopathologic response: 63 patients with EGF +61 G allele (AG + GG) had a 25% rate of pCR whereas the 50 patients with AA genotype had only a 2% rate of pCR (p < 0.001). In addition, the pCR rate of 69 patients with any 2R repeats in the TS 5'UTR (2R/2R + 2R/3R) was 20% while it was 0% in the 23 patients with the 3R/3R genotype (p = 0.006). Conclusions: This study suggests EGF A+61G and TS 5'UTR 2R/3R polymorphisms to be predictive markers for complete pathologic response to cetuximab-based neoadjuvant chemoradiation of patients with locally advanced rectal cancer. Author Disclosure Employment or Leadership Position Consultant or Advisory Role Stock Ownership Honoraria Research Funding Expert Testimony Other Remuneration Bristol-Myers Squibb, ImClone Systems, Merck Bristol-Myers Squibb, ImClone Systems, Merck, Merck Serono, Roche, sanofi-aventis Merck, Roche, sanofi-aventis
Sertraline for Preventing Mood Disorders Following Traumatic Brain Injury
Authors: Ricardo E. Jorge, Laura Acion, Debora I. Burin, Robert G. Robinson
Journal: JAMA Psychiatry (2016)

<h3>Importance</h3> Prevention is more effective than treatment to decrease the burden of significant medical conditions such as depressive disorders, a major cause of disability worldwide. Traumatic brain injury (TBI) is a candidate for selective strategies to prevent depression given the incidence, prevalence, and functional effect of depression that occurs after TBI. <h3>Objective</h3> To assess the efficacy of sertraline treatment in preventing depressive disorders following TBI. <h3>Design, Setting, and Participants</h3> A double-blind, placebo-controlled, parallel-group randomized clinical trial was conducted at a university hospital from July 3, 2008, to September 17, 2012, with 24 weeks of follow-up. A consecutive sample of 534 patients aged 18 to 85 years, hospitalized for mild, moderate, or severe TBI, was eligible for the study. Ninety-four patients consented to participate and were randomized (46 to placebo and 48 to sertraline), of whom 79 (84%) completed the study. Intention-to-treat data analysis was conducted from July 1, 2014, to December 31, 2015. <h3>Interventions</h3> Placebo or sertraline, 100 mg/d, for 24 weeks or until development of a mood disorder. <h3>Main Outcomes and Measures</h3> Time to onset of depressive disorders, as defined by the<i>DSM-IV</i>, associated with TBI. <h3>Results</h3> Of the 94 patients in the study (38 female and 56 male; 92 white), the number needed to treat to prevent depression after TBI at 24 weeks was 5.9 (95% CI, 3.1-71.1; χ<sup>2</sup> = 4.6;<i>P</i> = .03) for sertraline treatment vs placebo. The influence of sertraline in the course of neuropsychological variables was not detected. The intervention was well tolerated, and adverse effects were mild in both the sertraline and placebo groups. <h3>Conclusions and Relevance</h3> Sertraline appears to be efficacious to prevent the onset of depressive disorders following TBI. Future studies should replicate these findings in a large sample of patients with TBI and depict their long-term physical, cognitive, behavioral, and functional outcomes. <h3>Trial Registration</h3> clinicaltrials.gov Identifier:NCT00704379
Recessive Congenital Methaemoglobinaemia: Three New Mutations in the NADH-Cytochrome b5 Reductase Gene.
Authors: Elisa Fermo, Paola Bianchi, Cristina Vercellati, Anna P. Marcello, Wilma Barcellini, Ornella Marangoni, Massimo Garatti, Alberto Zanella
Journal: Blood (2006)
Hepatitis C Virus—From Discovery to Cure
Authors: Ralf F. W. Bartenschlager, Charles M. Rice, Michael J. Sofia
Journal: JAMA (2016)

In this Viewpoint, 2016 Lasker Award winners Ralf Bartenschlager, Charles Rice, and Michael Sofia discuss their work developing a system to study the replication of hepatitis C virus and a class of antivirals to treat the infection.
Gluteal rhabdomyolysis and renal failure due to simvastatin and amiodarone
Authors: Mariam Semmo, Nasser Abdalla Dhayat
Journal: Kidney International (2016)

A 54-year-old man on anticoagulation therapy with phenprocoumon was referred for suspicion of spontaneous gluteus muscle hematoma under therapy with phenprocoumon. He had woken up the day before with debilitating pain in the gluteal region and was not able to rise from his bed. The patient was fully conscious and could not recall any recent trauma; however, he mentioned that the day before the pain occurred, he made telephone calls in a sitting position for 2 hours to make funeral arrangements for his mother. The patient’s medical history was remarkable for cardiac surgery 4 years previously with coronary artery bypass grafting and aortic valve replacement, and for atrial fibrillation. Clinical examination revealed tender and tense swelling of his buttocks. Intravenous contrast computed tomography scans (Figure 1) and a lumbar magnetic resonance imaging scan revealed edematous swellings of the gluteus maximus but ruled out hematoma. The patient was anuric with a plasma creatinine of 344 μmol/l and a creatine kinase of 57,270 U/l. A circumscribed gluteal rhabdomyolysis with acute renal failure was diagnosed. Assessment of the myotoxicity of the patient's medication revealed that amiodarone was added to the previously well-tolerated long-term therapy with simvastatin 4 months before hospitalization. Both medications were discontinued, and, with alkaline diuresis, urine output increased to > 400 ml/2 hours, and within 4 days plasma creatinine improved to 90 μmol/l and creatine kinase to 5968 U/l. An increased risk of rhabdomyolysis with simvastatin and concomitant use of CYP3A4 inhibitors such as amiodarone is described in the literature. However, the isolated occurrence of gluteal rhabdomyolysis in this patient is a rare condition and may have been triggered by prolonged sitting.
Randomized phase II study of S-1 and concurrent radiotherapy with versus without induction chemotherapy of gemcitabine for locally advanced pancreatic cancer (JCOG1106).
Authors: Akira Fukutomi, Junki Mizusawa, Hiroshi Katayama, Satoaki Nakamura, Yoshinori Ito, Nobuyoshi Hiraoka, Tatsuya Ioka, Makoto Ueno, Masafumi Ikeda, Kazuya Sugimori, Kyoko Shimizu, Takuji Okusaka, Masato Ozaka, Hiroaki Yanagimoto, Shoji Nakamori, Takeshi Azuma, Ayumu Hosokawa, Naohiro Sata, Tetsuya Mine, Junji Furuse
Journal: Journal of Clinical Oncology (2015)

4116 Background: Most patients (pts) with locally advanced pancreatic cancer (LAPC) are treated with chemotherapy (CT) alone in Japan. Chemoradiotherapy (CRT) is also a treatment option, but the role of radiotherapy (RT) remains controversial. Recently, induction CT followed by CRT is recognized as one potentially promising strategy. The aim of this study is to evaluate the efficacy and safety of CRT with and without induction CT to determine which is more promising CRT strategy. Methods: LAPC pts with an ECOG PS of 0-1, aged 20-80, and adequate organ function were randomized to CRT (Arm A) or induction CT followed by CRT (Arm B). Pts in Arm A received RT (50.4 Gy/28 fr over 5.5 weeks) with concurrent S-1 (40 mg/m²/dose, b.i.d. on the day of irradiation). Pts in Arm B received induction gemcitabine (GEM) (1,000 mg/m², iv, days 1, 8 and 15, every 4 weeks) for 12 weeks, and then, only pts with controlled disease received same CRT as Arm A. After CRT, GEM was continued until disease progression or unacceptable toxicity in both arms. Primary endpoint was overall survival (OS). The sample size was 100 to detect ≥10% difference in 1-year OS with a probability of at least 0.9. Arm B will be considered to be more promising if point estimate of hazard ratio (HR) of OS for Arm B to Arm A is smaller than 1.186. Results: From 12/2011 to 9/2013, 102 pts were randomized, but 2 pts were ineligible because of metastasis. Therefore, 100 pts (Arm A/B n=51/49) were evaluated in this analysis. 50 pts received CRT in Arm A, while 34 pts in Arm B. 1-year OS for Arm A/B were 66.7/69.3% (HR 1.16 [95%CI 0.71-1.89]; p=0.56), and 1-year PFS were 39.2/46.6% (HR 1.05 [0.68-1.61]; p=0.84). Incidences of grade 3/4 toxicities in Arm A/B were leukopenia 62/61%, neutropenia 54/57%, anemia 18/12%, thrombocytopenia 10/14%, anorexia 16/4%, fatigue 8/4%, nausea 8/2%, diarrhea 6/4%, gastroduodenal (GD) hemorrhage 8/6%, GD ulcer 6/4%, and biliary infection 20/27%. Two treatment-related deaths occurred in Arm A (pneumonitis, duodenal hemorrhage). Conclusions: Induction CT followed by CRT was considered more promising as the test arm for a subsequent phase III trial comparing with CT alone. Clinical trial information: 000006811.
P1-252: Epoetin beta treatment for anemia in lung cancer patients under chemotherapy: results of a large prospective cohort study
Authors: Frederique Giraud, Toufik Didi, David Planchard, Pascal Foucher, Alain Ducolone, Jean-Philippe Oster, Roland Poirier, David Pau, Arash Jenabian
Journal: Journal of Thoracic Oncology (2007)
Real-world analysis of treatment patterns examining nab-Paclitaxel plus gemcitabine (nab-P+G) versus gemcitabine monotherapy (G) in first-line treatment of metastatic pancreatic adenocarcinoma (MPAC) in a U.S. community oncology setting.
Authors: Fadi S. Braiteh, Manish Patel, Monika Parisi, Quanhong Ni, Si yeon Park, Claudio Faria
Journal: Journal of Clinical Oncology (2016)

e18100 Background: Based on a randomized clinical trial, MPACT, nab-P+G had superior overall survival (OS) compared to G for the treatment of advanced PAC, but limited data is available comparing the effectiveness of these treatment options in a real-world setting. The objective of this study is to compare treatment patterns of patients (pts) receiving nab-P+G versus G for first-line treatment of MPAC. Methods: A retrospective cohort study was performed using fully de-identified data from a nationally representative electronic medical record platform of 1,300 community oncologists. Pts diagnosed with MPAC between September 2013 and October 2014 and received 1st line therapy with either nab-P+G or G were included in the analysis. We calculated the median time to treatment discontinuation (TTD) and estimated survival (ES), a proxy for OS, using the Kaplan Meier method, and assessed incidence of adverse events (AEs) and supportive care usage. We carried out a sensitivity analysis on patients aged 70 and above for TTD and ES. Results: Out of 851 pts, 168 met eligibility criteria (nab-P+G, n = 122; G, n = 46). Pts in the nab-P+G arm were younger (mean age 67.0 v 72.0, p < 0.01) and mostly males (60% v 44%). Other baseline characteristics were comparable. nab-P+G pts had a statistically significant longer median TTD (3.4 v 2.2 mos; p < 0.01) and median ES (8.6 v 5.3 mos, p = 0.03). For pts > 70, TTD and ES were longer in the nab-P+G group compared to the G group (3.7 mos v 2.1 mos, p = 0.02; 8.2 v 5.2 mos, p = 0.02). nab-P+G pts had fewer AEs-related to discontinuation (18% v 26%); but utilized more doses of G-CSF (2.02 v 0.73, p < 0.01), ESA (0.90 v 0.54, p < 0.01) and steroids (7.89 v 0.58 doses, p < 0.01) per 100 days compared to pts on G. Conclusions: Similar to the benefit demonstrated in MPACT trial comparing nab-P+G with G,patients receiving nab-P+G experienced significantly longer median TTD and ES in this real-world analysis vs G. More supportive care may have been used in the nab-P+G group due to longer treatment duration.
Clinical outcomes of melanoma brain metastases treated with stereotactic radiosurgery and anti-PD-1 therapy, anti-CTLA-4 therapy, BRAF/MEK inhibitors, BRAF inhibitor, or conventional chemotherapy
Authors: K.A. Ahmed, Y.A. Abuodeh, M.I. Echevarria, J.A. Arrington, D.G. Stallworth, C. Hogue, A.O. Naghavi, S. Kim, Y. Kim, B.G. Patel, S. Sarangkasiri, P.A.S. Johnstone, S. Sahebjam, N.I. Khushalani, P.A. Forsyth, L.B. Harrison, M. Yu, A.B. Etame, J.J. Caudell
Journal: Annals of Oncology (2016)
P1-067: Prognosis of small adenocarcinoma of the lung based on thin-section CT and pathological preparations
Authors: Mizuki Ikehara, Haruhiro Saito, Kouzo Yamada, Fumihiro Oshita, Kazumasa Noda, Haruhiko Nakayama, Kazuo Masui, Yoichi Kameda, Yuko Komase, Teruomi Miyazawa
Journal: Journal of Thoracic Oncology (2007)
Exenatide once weekly plus dapagliflozin once daily versus exenatide or dapagliflozin alone in patients with type 2 diabetes inadequately controlled with metformin monotherapy (DURATION-8): a 28 week, multicentre, double-blind, phase 3, randomised controlled trial
Authors: Juan P Frías, Cristian Guja, Elise Hardy, Azazuddin Ahmed, Fang Dong, Peter Öhman, Serge A Jabbour
Journal: The Lancet Diabetes & Endocrinology (2016)
Atrial-specific pathways for control of intracellular signaling and myocyte function
Authors: Thomas J. Hund, Peter J. Mohler
Journal: Journal of Clinical Investigation (2016)

Atrial fibrillation (AF) is a cardiac arrhythmia that arises from electrical and contractile dysfunction in the atria. Atrial function is regulated by a variety of intracellular signaling networks that facilitate rapid communication and coordinate responses of atrial myocytes. In this issue of the JCI, Brandenburg and colleagues describe the identification and characterization of "super-hub" signaling nodes located on atrial axial tubules that regulate atrial contraction. Together, the results of this study provide important insight into the regulation of atrial contraction and describe potential therapeutic targets to be explored in future studies.
P3-175: Prediction of radiation pneumonitis by dose-volume histogram parameters, especially focused on main bronchus
Authors: Takeshi Ebara, Hidemasa Kawamura, Hitoshi Ishikawa, Tetsuo Nonaka, Hiroki Kiyohara, Masaru Wakatsuki, Hideyuki Sakurai, Takashi Nakano
Journal: Journal of Thoracic Oncology (2007)
Phase II window of irinotecan plus carboplatin in newly diagnosed patients with rhabdomyosarcoma: Results of Memorial Sloan-Kettering Cancer Center (MSKCC) Protocol IRB 03-099.
Authors: L. H. Wexler, S. L. Wolden, S. J. Abramson, A. Price, S. Karimi, M. P. La Quaglia, A. J. Chou, P. R. Merola, P. A. Meyers
Journal: Journal of Clinical Oncology (2010)

9533 Background: There has been little improvement in outcome for patients (pts) with intermediate (INT)- and high-risk (HR) rhabdomyosarcoma (RMS) in nearly 2 decades. Methods: From November 2003 through December 2009, we enrolled 56 newly diagnosed pts with INT- (28) and HR (28) RMS on IRB 03-099, a 7-drug regimen that commenced with 2 courses of irinotecan + carboplatin (I+C) given 3 weeks apart. I (20 mg/m2 IV over 1 hour) was given on days 1-5 and 8-12; C (560 mg/m2 IV over 1 hour) was given on day 1. Results: Median age at diagnosis was 11.5 yrs (4 months – 42 years); median tumor size was 6 cm. There were 29 males and 27 females; 30 pts (15 HR) had alveolar RMS (ARMS); 24 pts (12 HR) had embryonal RMS (ERMS); one each had sclerosing RMS and pleomorphic RMS (HR RMS). Of 28 pts with INT-RMS, 26 had invasive (T2) and/or 16 large (Tb) tumors, and 15 were N1. 11 of 28 pts with HR RMS had more than 1 site of metastatic disease. Pts were restaged after 2 cycles using RECIST and WHO response criteria. 4 pts were inevaluable for response (3 Group IIa, 1 Group IIc); all were evaluable for toxicity. Week 6 responses were: 3 CR, 32 PR, 17 SD, and 0 PD. All 9 ARMS pts with bone marrow involvement had resolution of disease by week 6 by RT-PCR. Hospitalizations occurred in 51 of 112 cycles primarily for management of GI toxicities and/or febrile neutropenia. Conclusions: The combination of I+C is strikingly active in pts with newly diagnosed INT- and HR RMS. GI and hematologic toxicities are significant but manageable. The role of I+C in the management of newly diagnosed INT- and HR RMS pts is worthy of further exploration. No significant financial relationships to disclose.
PD6-3-3: Medical and economical impact of bone metastases in lung cancer patients: a prospective French national, multicentric study (GFPC 06-01 study)
Authors: Chantal Decroisette, Isabelle Monnet, Suzanna Bota, Laurence Bigay-Game, Herve Le Caer, Henri Berard, Philippe David, Clarisse Audigier-Valette, Laurence Geriniere, Christos Chouaid
Journal: Journal of Thoracic Oncology (2007)
P3-013: K-ras codon 12 mutations in Non Small Cell Lung Cancer: high incidence of mutations in endobronchial tissue
Authors: Pablo Moreno Acosta, Omaira Barba Rueda, Clara Espinel, Alfredo Romero, Plutarco García Herreros, Monica Molano Luque, Diana Mercedes Ramirez Gómez
Journal: Journal of Thoracic Oncology (2007)
Risk factors for endocarditis after transcatheter aortic valve replacement are identified
Authors: Jacqui Wise
Journal: BMJ (2016)

Researchers have identified a number of risk factors associated with an increased risk of infective endocarditis after transcatheter aortic valve replacement.

Research published in JAMA shows that, among patients undergoing transcatheter aortic valve replacement, younger age, male sex, history of diabetes mellitus, and moderate to severe aortic regurgitation were all associated with an increased risk of endocarditis.1 Patients who developed endocarditis had high rates of in-hospital mortality and two year mortality, the study found.

Transcatheter aortic valve replacement involves inserting a catheter into a blood vessel in the upper leg or chest and passing it towards …