tbuckley/cabot-search huggingface dataset:
Over-the-scope clips for transoral gastric outlet reduction as salvage therapy for weight regain after Roux-en-Y gastric bypass
Authors: Vivek Kumbhari, Jennifer Cai, Alan Tieu, Anthony Kalloo, Mouen Khashab
Journal: Endoscopy (2015)

A 49-year-old man was referred for management of weight regain 3 years after Roux-en-Y gastric bypass (RYGB) surgery. He had gained 14 kg in weight in the previous 6 months. Upper endoscopy revealed a 35-mm gastrojejunal anastomosis. Three sessions of transoral gastric outlet reduction over 7 months using endoscopic suturing (OverStitch; Apollo Endosurgery, Austin, Texas, USA) had not resulted in any response. After discussion with the bariatric surgeon, it was decided that gastrojejunal anastomosis reduction using the "type t" over-the-scope clip (OTSC) (Ovesco AG, Tubingen, Germany) would be trialed before redo surgery [1].
Relationship of circulating hyaluronic acid levels to disease control in asthma and asthmatic pregnancy
Authors: István Ivancsó, Noémi Eszes, Gabriella Beko, Anikó Bohács, Gergely Toldi, János Rigó, György Losonczy, Barna Vásárhelyi, Lilla Tamási
Journal: European Respiratory Journal (2013)

Asthma has a high burden of morbidity if not controlled and frequently complicates pregnancy posing a risk for complications. Serum hyaluronic acid (HA) is an acknowledged marker of tissue fibrosis which promotes eosinophil survival and plays a role in airway remodeling. Although circulating HA is easily measurable, and its role is supposed in asthmatic inflammation, tissue remodelling and maintenance of normal pregnancy as well, to date there are no data on its levels in asthmatic pregnancy. The possible relationship of circulating HA levels and clinical asthma control is also unknown.  The aim of this study was to evaluate the serum levels of HA in asthmatic pregnant (AP; N=17) and asthmatic non-pregnant (ANP; N=42) patients. The possible relationship between HA levels and asthma control determinants (spirometry, symptoms) was also evaluated.  Serum HA level was lower in AP than in ANP patients (27 [24.8-36.4] vs. 36.3 [27.35-52.60] ng/mL, p=0.026). A positive correlation was found between HA and airway resistance in ANP (r=0.3684, p=0.019) but not in AP patients. ROC analysis of HA values in asthmatic patients with Asthma Control Test total score above and below 20 yielded an AUC of 0.74 (95% CI: 0.58-0.90, p=0.015) and identified an optimal cut-off value of 25.8 ng/mL between controlled and not controlled asthmatic patients.  Serum HA might be a marker of asthma control, since it correlates with airway resistance and has good sensitivity in the detection of impaired asthma control. Lower circulating HA level detected in pregnant than in non-pregnant asthmatics may be the consequence of pregnancy induced immune tolerance and attenuated systemic inflammatory responses.
Oral analgesia and anxiolysis for pain associated with bone marrow biopsy
Authors: G. Talamo, W. Zhang, M. Bayerl
Journal: Journal of Clinical Oncology (2008)

20605 Background: Bone Marrow aspiration and biopsy (BMAB) is an invasive procedure commonly performed for the diagnosis of blood disorders and solid tumors. We evaluated the effectiveness of a combination of oral analgesics and minimal sedation (anxiolysis) in reducing the pain score of patients undergoing BMAB. Methods: Our study was retrospective and non-randomized. Seventy-eight consecutive adult patients (pts) underwent BMAB performed by a single physician in the left posterior superior iliac crest, using 5 mL of lidocaine HCl 1% solution (= 50 mg total dose) as local anesthesia in all pts. Thirty-three pts received preemptive analgesia with acetaminophen 650 mg and oxycodone 10 mg, and concomitant anxiolysis with lorazepam 2 mg. Drugs were given orally 30 minutes before the procedure. To assess the degree of pain, we used the Wong-Baker Faces Pain Rating Scale, which distinguishes 11 levels of pain, from 0 to 10. Results: The median pain level of the overall group was 3.5 (± 2.8). Among 45 pts treated with local anesthesia alone, median pain level was 4.0 (range 0–10, SD 2.9), and among 33 pts treated with additional analgesia and anxiolysis, median pain level was 2.9 (range 0–10, SD 2.3) (p>0.05). Statistical analysis did not find a correlation between pain score and several factors, including age, sex, weight, and length of specimen. No hemodynamic or respiratory complications were observed in the group receving analgesia and anxiolysis. Conclusions: The preemptive use of oral lorazepam, acetaminophen, and oxycodone, at the above doses, did not produce a clinically significant reduction of the perception of pain during BMAB. No significant financial relationships to disclose.
Persistence of HER2 overexpression on circulating tumor cells in patients after systemic treatment for HER2-positive breast cancer: Follow-up results of the German Success B trial.
Authors: Julia Katharina Neugebauer, Brigitte Kathrin Rack, Bernadette Anna Sophia Jaeger, Ulrich Andergassen, Aurelia Pestka, Peter A. Fasching, Thomas W. P. Friedl, Doraid Mouarrawy, Michael R. Clemens, Gabriele Ziemendorff, Georg Heinrich, Ekkehard von Abel, Andreas Schneeweiss, Matthias W. Beckmann, Klaus Pantel, Wolfgang Janni
Journal: Journal of Clinical Oncology (2013)

11043 Background: The discordance between HER2-expression on circulating tumor cells (CTC) in peripheral blood and the primary tumor has already been shown by our study group for early breast cancer patients with HER2-positive tumors. Here, we compare the results to CTC prevalence and HER2-status of CTC after adjuvant chemotherapy. Methods: The SUCCESS B trial compares FEC-Docetaxel vs. FEC-Docetaxel-Gemcitabine and HER2-targeted therapy as adjuvant treatment for patients with early, HER2-positive, node positive or high risk node negative primary breast cancer. We prospectively analyzed 23ml peripheral blood before and after chemotherapy. CTC and HER2-status were assessed with the CellSearchSystem (Veridex, USA). After immunomagnetic enrichment with an anti-Epcam-antibody, cells were labeled with anti-CK 8/18/19, anti-CD45 antibodies as well as a fluorescein conjugate antibody for HER2-phenotyping. Cutoff for CTC positivity was ≥ 1 CTC. HER-positivity of CTC was assigned if at least one CTC showed strong HER2 staining (3+). Results: CTCs and their HER2-status both before and after chemotherapy were available for 392 patients. In 179 (45.7%) patients no CTC were detected before and after chemotherapy. CTC status changed from positive before to negative after chemotherapy in 104 (26.5%) patients and from negative before to positive after chemotherapy in 69 (17.6%) patients, while 40 (10.2%) patients had a consistently positive CTC status. Patients were significantly more likely to change their CTC status from positive to negative than from negative to positive (p = 0.01). Of the 40 patients with CTC both before and after chemotherapy, 14 (35%) patients had HER2-positive CTC before and after therapy, and 9 (22%) patients had HER2-negative CTC at both time points. 7 (18%) patients had HER2-positive CTC before but not after chemotherapy, while 10 (25%) patients showed the reverse pattern (p = 0.63). Conclusions: Cytotoxic treatment does not seem to influence the HER2-status on CTC. Follow-up data within the Success B trial will analyze the relevance of the HER2-expression of CTC to predict the efficacy of targeted treatment.
Association of <i>helicobacter pylori</i> CagA translocation with the expression of CagA-signaling transduction molecules in gastric mucosa-associated lymphoid tissue lymphoma.
Authors: Sung Hsin Kuo, Li-Tzong Chen, Chung-Wu Lin, Ping-Ning Hsu, Ming-Shiang Wu, Hui-Jen Tsai, Yi-Shin Tzeng, Kun-Huei Yeh, Ann-Lii Cheng
Journal: Journal of Clinical Oncology (2014)

8571 Background: We previously reported that a direct contact of Helicobacter pylori (HP) with B cells results in CagA translocation into the latter, and the translocated CagA regulates intracellular signaling pathways. Toward this end, we recently found that CagA do exist in the malignant B cells of gastric mucosa-associated lymphoid tissue (MALT) lymphoma, and its presence is closely associated with HP-dependence. In this study, we further evaluate whether CagA expression regulates signaling transduction molecules in tumor cells of HP-positive gastric MALT lymphoma. Methods: Forty-seven patients of stage IE HP-positive gastric MALT lymphoma, who received HP eradication as their frontline therapy, were included. The expression of CagA, and its signaling pathway-related proteins, such as phosphorylated-SHP-2 (p-SHP-2), p-ERK, p-p38MAPK, Bcl-2, and Bcl-xL in tumor cells were evaluated by immunohistochemistry. Results: There were 25 HP-dependent and 22 HP-independent cases. Expression of CagA was closely associated with p-SHP-2 (P = .012), p-ERK (P =.002), p-p38MAPK (P = .006), Bcl-2 (P = .020, and Bcl-xL (P = .006) expression. Spearman’s correlation coefficient analysis showed the strong correlation between CagA-signaling transduction molecules. Combined CagA expression, p-SHP-2 expression and p-ERK expression showed an increased positive predictive value (93.3% [14/15] versus 81.8% [18/22]) and an increased specificity (95.5% [21/22] versus 81.8% [18/22]) for HP-dependence than CagA expression alone. Conclusions: Our results indicate that the expression of CagA protein is biologically active and is associated with activation of its downstream signals of HP-dependent gastric MALT lymphoma.
Low Skeletal Muscle Density is Predictive for Febrile Neutropenia in Patients Treated By Doxorubicin/Trabectedin/Pegfilgrastim Combination As a First-Line Treatment of Advanced or Metastatic Leiomyosarcoma (Lms) (Lms02 Study)
Authors: S. Antoun, A. Floquet, C. Chevreau, N. Penel, C. Delcambre, D. Cupissol, N. Isambert, J. Alexandre, B. Lacas, P. Pautier
Journal: Annals of Oncology (2014)
Abstract 16305: Microbubble and Ultrasound Mediated Thromboprophylaxis in Porcine Models of Extracardiac Shunts
Authors: Shelby Kutty, Juefei Wu, James M Hammel, Joseph R Abraham, Jeeva Venkatarman, Ibrahim Abdulla, John Lof, Stanely J Radio, Thomas R Porter
Journal: Circulation (2013)

Background: Palliative shunts in congenital heart disease patients are vulnerable to thrombotic occlusion. High mechanical index (MI) impulses from a modified diagnostic ultrasound (US) transducer ...
Association of maintenance rituximab with clinical outcome in rituximab-naïve patients with Waldenstrom's macroglobulinemia (WM) who respond to a rituximab-containing regimen.
Authors: L. I. Ioakimidis, C. A. Hanzis, R. J. Manning, C. J. Patterson, J. D. Soumerai, Z. R. Hunter, P. S. Brodsky, P. S. Sheehy, B. Turnbull, S. P. Treon
Journal: Journal of Clinical Oncology (2010)

8107 Background: Rituximab alone and in combination is an important mainstay of therapy for WM. While maintenance rituximab (MRx) is often employed after induction therapy, its safety and efficacy has not been investigated in WM. Methods: We therefore investigated the outcome of 248 rituximab-naive WM patients who responded to a rituximab-based induction therapy, including 86 (35%) patients who then received MRx. No differences in baseline characteristics, and post-induction categorical responses were observed between cohorts. Induction therapy included rituximab alone (n=79) or in combination (n=169). The median rituximab infusions during induction was 6 for both cohorts; and 8 over a 2 year period for MRx treated patients. Results: With a median follow-up of 37.9 months, categorical response upgrade occurred in 16/162 (10%) versus 36/86 (41.8%) of observed and MRx treated patients, respectively (p<0.0001). The median PFS for MRx treated patients was 56.3 versus 28.6 months for observed patients (p=0.0001). Improved PFS was observed despite previous treatment status (p≤0.001); induction with rituximab alone (p=0.001), or in combination therapy (p=0.0001). Among patients receiving MRx therapy, the median OS was >120 months versus 116 months for patients who were observed (p=0.0095). Improved OS was observed despite previous treatment status (p≤0.001), induction with rituximab alone (p=0.083) or in combination (p=0.041). No difference in PFS and OS for patients was observed between patients who received MRx as 1 single infusion every 3 months versus 4 weekly infusions every 6 months (p=0.49 and 0.38, respectively). 20.4% and 38.4% of observed and MRx patients experienced at least 1 infectious event, respectively (p=0.0064). Most infections involved the sinus and pulmonary tracts; all but 6 of these events were (p = 0.718). Conclusions: MRx is well tolerated and associated with improved clinical outcomes in WM patients who respond to induction with a rituximab-containing regimen despite previous treatment status, treatment with rituximab alone, or in combination therapy. Author Disclosure Employment or Leadership Position Consultant or Advisory Role Stock Ownership Honoraria Research Funding Expert Testimony Other Remuneration Biogen Idec, Celgene, Genentech, Millennium Biogen Idec, Celgene, Millennium Celgene, Millennium
Triple induction chemotherapy and chemoradiotherapy in locally advanced esophageal cancer: Final results of a multicenter phase II trial
Authors: W. M. Eisterer, A. De Vries, B. Spechtenhauser, D. Kendler, A. Königsrainer, H. Nehoda, P. Lukas, E. Wöll, D. Öfner
Journal: Journal of Clinical Oncology (2007)

4568 Background: Surgery is the standard treatment for patients with resectable esophageal carcinoma, but 5-year survival rates rarely exceed 20%. Neoadjuvant chemoradiotherapy (CRT) may lead to downstaging of the tumor and thus improve the possibility of complete oncologic resection. Docetaxel (Dx) showed considerable activity in combination with hyperfractionated radiotherapy and only moderate toxicity. We evaluated a triple neoadjuvant regime including Dx in patients with locally advanced esophageal adenocarcinoma (AC) or squamos cell carcinoma (SCC). Methods: 24 patients (pts) with AC (n=8) or SCC (n=16) medically fit, no prior therapy, ECOG-performance status = 2 were included. Pts received 2 cycles of cisplatin (Cis) 15mg/ms 2 d1–5, 5-fluorouracil (5-FU) 750mg/m 2 continuous infusion (CI) d1–5, and Dx 75mg/m 2 d1 repeated every 29 days followed by radiotherapy (RT) 39.6 Gy total dose (daily fraction 1.8Gy) concomitant to Dx 15mg/m 2 on days 1, 8, 15, 22 and 5-FU 300mg/m 2 CI on the days of RT followed by resection or definitive RT up to 59.6 Gy in case of inoperability. Results: See table . Grade 3/4 toxicity (n/%): neutropenia 10/43%, diarrhea 4/18%, alopecia 2/9%; deep vein thrombosis 1/5%, blurred vision 1/5%, fever 1/5%, pulmonary embolus 1/5%, arterial hypertension 1/5%. 1 pt died 39 days post resection due to fatal anastomical bleeding. 6/16 operated pts (37%) showed morbidity (anastomical stenosis/insufficiency, fistula, nervus recurrens palsy). 4/22 pts (18%) died 7- 25 months after therapy due to metastatic disease. At a median follow-up of 12 months 18 pts (82%) are alive, median survival has not been reached yet. Conclusions: Triple induction CT and CRT with Dx, Cis, and 5-FU is safe, feasible, and effective with CPR in 31%, downstaging in 81% and R0-resection in 100% of pts. Main toxicities are neutropenia (43%) and postoperative morbidity (37%). A follow-up phase II trial of triple induction therapy in combination with an EGFR-directed antibody is planned. [Table: see text] No significant financial relationships to disclose.
Smoking-Attributable Mortality—Mexico, 1992
Journal: JAMA (1995)

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Antibiotic resistance in Enterobacteriaceae: mechanisms and clinical implications
Authors: Jon Iredell, Jeremy Brown, Kaitlin Tagg
Journal: BMJ (2016)

Resistance of the Enterobacteriaceae to antibiotics, especially of the β lactam type, is increasingly dominated by the mobilization of continuously expressed single genes that encode efficient drug modifying enzymes. Strong and ubiquitous selection pressure has seemingly been accompanied by a shift from “natural” resistance, such as inducible chromosomal enzymes, membrane impermeability, and drug efflux, to the modern paradigm of mobile gene pools that largely determine the epidemiology of modern antibiotic resistance. In this way, antibiotic resistance is more available than ever before to organisms such as <i>Escherichia coli</i> and <i>Klebsiella pneumoniae</i> that are important causes of major sepsis. Modulation of the phenotype by host bacteria makes gene transmission less obvious and may in part explain why tracking and control of carbapenem resistance has been particularly problematic in the Enterobacteriaceae. This review discusses the underlying principles and clinical implications of the mobility and fixation of resistance genes and the exploitable opportunities and potential threats arising from apparent limitations on diversity in these mobile gene pools. It also provides some illustrative paradoxes and clinical corollaries, as well as a summary of future options.
Does interruption of imatinib (IM) in responding patients after three years of treatment influence outcome of patients with advanced GIST included in the BFR14 trial?
Authors: A. Adenis, P. A. Cassier, B. N. Bui, M. Rios, F. Duffaud, F. Bertucci, S. Chabaud, D. Pérol, J. Y. Blay, A. Le Cesne
Journal: Journal of Clinical Oncology (2008)

10522 Background: We previously demonstrated that IM must not be interrupted after one year (yr) in responding patients (pts) and has to be given continuously until disease progression (PD) or intolerance (JCO 2007). The impact of treatment interruption at later time points on progression-free survival (PFS) and overall survival (OS) is unknown. Methods: This prospective national multicenter BFR14 study was initiated in June 2002. After 3 yrs of IM 400mg/day, pts free from progression were randomly offered to continue (C arm) or interrupt (I arm) IM, with the exception of pts initially randomized in the I arm after 1 yr of IM (32 pts). Pts allocated to the I arm could restart IM (same dose) in case of PD. Primary endpoint was PFS. Pts declining randomization proceed with IM. Results: As of December 2007, 378 pts were included in this trial. Fifty nonprogressive pts at 3 yrs were randomized, 25 and 25 in the I and C arm, respectively. Pt characteristics were well balanced between the two arms. After a median follow-up of 11.4 months (CI 95% = 7.4–14.7) the one yr PFS were 87.7 and 23.7% for C and I arms, respectively. IM reintroduction in the I arm after a re-progression allowed again a tumor control (OR or SD) in 100% evaluable pts so far. OS were similar in both arms: the one yr OS were 100 and 94.7% for C and I arms respectively. Time to secondary resistance to IM (TSRI) was not significantly different suggesting that TSRI starts to count at the date of first IM challenge. Conclusions: The majority of responding patients relapsed when IM was stopped after 3 yrs of treatment but GIST cells remain sensitive to IM at reintroduction. At the time of the present analysis, no impact of IM discontinuation on OS could be detected. Updated results including mutational analysis will be presented at the meeting. This work is supported by research funding from Novartis Pharma. Author Disclosure Employment or Leadership Consultant or Advisory Role Stock Ownership Honoraria Research Expert Testimony Other Remuneration GlaxoSmithKline, Novartis, Pfizer Oncology, PharmaMar Amgen, GlaxoSmithKline, Novartis, Pfizer Oncology, PharmaMar Novartis Bayer, Pfizer Oncology, sanofi-aventis
Cardiac adipose tissue and atrial fibrillation: the perils of adiposity
Authors: Stéphane N. Hatem, Alban Redheuil, Estelle Gandjbakhch
Journal: Cardiovascular Research (2016)

The amount of adipose tissue that accumulates around the atria is associated with the risk, persistence, and severity of atrial fibrillation (AF). A strong body of clinical and experimental evidence indicates that this relationship is not an epiphenomenon but is the result of complex crosstalk between the adipose tissue and the neighbouring atrial myocardium. For instance, epicardial adipose tissue is a major source of adipokines, inflammatory cytokines, or reactive oxidative species, which can contribute to the fibrotic remodelling of the atrial myocardium. Fibro-fatty infiltrations of the subepicardium could also contribute to the functional disorganization of the atrial myocardium. The observation that obesity is associated with distinct structural and functional remodelling of the atria has opened new perspectives of treating AF substrate with aggressive risk factor management. Advances in cardiac imaging should lead to an improved ability to visualize myocardial fat depositions and to localize AF substrates.
Galectin-1 stimulates 2-deoxyglucose uptake though Ca2+/PKC, p44/42 MAPKs, PI3K/Akt, and mTOR signal pathway in mouse embryonic stem cells
Authors: Min Young Lee, Yun Hee Kim, Sang Hun Lee, Han Na Suh, Yu Jin Lee, Jung Min Ryu, Seung Pil Yun, Jae Hong Park, Mi Ok Kim
Journal: Clinical Cancer Research (2007)

AACR Centennial Conference: Translational Cancer Medicine-- Nov 4-8, 2007; Singapore

C10 

The responsiveness of the glucose transporter to extracellular stimuli in embryos is an extremely important mechanism for providing more substrates to cope with the increased cellular demand arising from growth, proliferation, and differentiation. Galectin-1 regulates a wide variety of processes in embryogenesis. However, the precise role of galecitn-1 on the glucose metabolism in mouse embryonic stem (ES) cells is not completely understood. Therefore, this study investigated the effect of galectin-1 on the 2-deoxyglucose (2-DG) uptake and its related signal cascades in mouse ES cells. Galectin-1 significantly increased the level of 2-DG uptake in a time- (≥ 8 hr) and dose- (≥ 0.01 ng/ml) dependent manner. Moreover, galectin-1 increased glucose transporter (GLUT)-1 mRNA and protein expression levels, which were inhibited by a disruption in transcription by actinomycin D and translation by the cycloheximide. Subsequently, the galectin-1-induced 2-DG uptake were attenuated by these inhibitors. In investigation of signal transduction involved in this process, galectin-1 increased intracellular Ca2+ concentration ([Ca2+]i) and the PKC activation, which induced p44/42 MAPKs phosphorylation. On the other hand, in case that galectin-1 activated PI3K/Akt pathway, p44/42 MAPKs was not involved in this process. Moreover, mTOR signal pathway was stimulated in response to galectin-1. In experiment to examine the relationship between each pathway, mTOR phosphorylation was blocked by the inhibition of Ca2+/PKC, p44/42 MAPKs, and PI3K/Akt pathways, respectively. Finally, galectin-1-induced the increase of GLUT-1 expression and 2-DG uptake were inhibited by blocking of Ca2+/PKC, p44/42 MAPKs, PI3K/Akt, and mTOR pathways. In conclusion, galectin-1 up-regulates glucose uptake through Ca2+/PKC, p44/42 MAPKs, PI3K/Akt, and mTOR pathways in mouse embryonic stem cells.    Key words: Galectin-1, 2-deoxyglucose uptake, GLUT-1, mouse embryonic stem cells