tbuckley/cabot-search huggingface dataset:
Abstract 17014: Getting to Zero: Impact of Electroanatomical Mapping on Fluoroscopy Use in Pediatric Catheter Ablation
Authors: Bradley C Clark, Kohei Sumihara, Robert McCarter, Charles I Berul, Jeffrey P Moak
Journal: Circulation (2015)

Introduction: Over the past several years, alternative imaging techniques including electroanatomic mapping systems such as CARTO®3 (C3) have been developed to improve anatomic resolution and potentially limit radiation exposure in electrophysiology (EP) procedures. We retrospectively examined the effect of the introduction of C3 on patient radiation exposure during EP studies and ablation procedures at a children’s hospital. Methods: All patients that underwent EP and ablation procedures between January 2012 and November 2014 were included; demographic information, fluoroscopy time in minutes (FT), total radiation dose in mGy (RAD), and dose-area product in μGy/m2 (DAP) were collected. Patients were stratified by time period (before vs. after C3 introduction), structural group (normal heart, congenital heart disease (CHD), and those with normal cardiac anatomy requiring trans-septal (TS) access), and arrhythmia diagnosis (Accessory Pathway (AP), AV Nodal Reentry Tachycardia (AVNRT), atrial, or ventricular arrhythmia). Mean values were compared using a single sample t-test, as well as analysis of covariance to control for age, weight, and arrhythmia diagnosis. Results: Mean FT decreased after the introduction of C3 in patients with normal hearts (p&lt;0.001), AP (p&lt;0.001), AVNRT (p=0.002), and CHD (p=0.007). After controlling for age, weight, and arrhythmia diagnosis, there was a statistically significant decrease in FT in all three groups (normal heart, CHD and TS), in RAD in the TS group, and in DAP in both the normal heart and TS groups. In all other groups, there was a trend towards decreased RAD and DAP, but they did not reach statistical significance. After the introduction of C3, zero fluoroscopy was achieved in 18/66 (27%) and ≤ 1 minute of FT in 28/66 (42%) of ablation procedures in patients with normal hearts. Conclusions: We have shown a decrease in all metrics that measure radiation exposure when comparing the time periods before and after the introduction of C3, secondary to reducing fluoroscopy time, fluoroscopic pulse rate and radiation dose per pulse. Further refinements are still needed to decrease radiation exposure towards the goal of zero fluoroscopy, but this cannot be achieved without thinking beyond fluoroscopy time.
Development of a practice consensus statement of the management of locally advanced breast cancer: Expert consensus and systematic review.
Authors: Robyn Leonard, Sophie Hogeveen, Dolly Han, Audrey Wong, Jalal Ebrahim, Yanchini Rajmohan, Jean-Francois Boileau, Sonal Gandhi, Justin Lee, Robert Edward Dinniwell, Muriel Brackstone, Christine E. Simmons
Journal: Journal of Clinical Oncology (2013)

e17526 Background: For locally advanced breast cancer patients (LABC), there are currently limited, if any, up-to-date protocol guidelines. The objective of this paper was to develop a consensus of opinion amongst Canadian oncologists, and to determine if Canadian oncologists agreed with the relevant literature. Methods: A modified Delphi survey protocol was used to determine consensus of opinion amongst 83 Canadian experts identified by peers as leaders in LABC. Consensus was defined as &gt; 85% agreement. Concurrently, a systematic review of the literature was performed to identify randomized controlled trials (RCTs) in this field (limits imposed were “humans”, “English language” and “RCT”). The protocols utilized in the RCTs were compared to the results of the consensus survey to determine if expert opinion in Canada is evidence-based or experiential. Results: Consensus of opinion amongst experts was obtained across all areas of patient management except for use of MRI in the workup of patients with LABC. 81% stated MRI would be required prior to initiation of therapy and 68% stated repeat MRI would be required prior to surgical planning in cases where lumpectomy is considered an option. Expert consensus reflected the published literature well in the areas of: clinical assessment with caliper at each cycle, option of lumpectomy if good clinical response, radiotherapy to loco-regional lymph nodes, and no further adjuvant chemotherapy outside of a clinical trial if residual disease is found at the time of surgery. On most other aspects of patient management the Canadian consensus was more conservative than the published literature, except for the use of salvage radiotherapy in the setting of progression on therapy, where the literature was more conservative than the Canadian opinion. Conclusions: A national practice consensus has been developed for the management of LABC which reflects the published literature or is more conservative than the published literature. The only area of clinical equipoise nationally is on the utility of MRI both pre and post neoadjuvant therapy. A further study assessing the appropriate role of MRI clinically in the treatment of LABC patients is warranted.
Temporal muscle thickness is an independent prognostic marker in patients with progressive glioblastoma: translational imaging analysis of the EORTC 26101 trial
Authors: Julia Furtner, Els Genbrugge, Thierry Gorlia, Martin Bendszus, Martha Nowosielski, Vassilis Golfinopoulos, Michael Weller, Martin J van den Bent, Wolfgang Wick, Matthias Preusser
Journal: Neuro-Oncology (2019)

Temporal muscle thickness (TMT) was described as a surrogate marker of skeletal muscle mass. This study aimed to evaluate the prognostic relevance of TMT in patients with progressive glioblastoma.TMT was analyzed on cranial MR images of 596 patients with progression of glioblastoma after radiochemotherapy enrolled in the European Organisation for Research and Treatment of Cancer 26101 trial. An optimal TMT cutoff for overall survival (OS) and progression-free survival (PFS) was defined in the training cohort (n = 260, phase II). Patients were grouped as "below" or "above" the TMT cutoff and associations with OS and PFS were tested using the Cox model adjusted for important risk factors. Findings were validated in a test cohort (n = 308, phase III).An optimal baseline TMT cutoff of 7.2 mm was obtained in the training cohort for both OS and PFS (area under the curve = 0.64). Univariate analyses estimated a hazard ratio (HR) of 0.54 (95% CI: 0.42, 0.70; P < 0.0001) for OS and an HR of 0.49 (95% CI: 0.38, 0.64; P < 0.0001) for PFS for the comparison of training cohort patients above versus below the TMT cutoff. Similar results were obtained in Cox models adjusted for important risk factors with relevance in the trial for OS (HR, 0.54; 95% CI: 0.41, 0.70; P < 0.0001) and PFS (HR, 0.47; 95% CI: 0.36, 0.61; P < 0.0001). Results were confirmed in the validation cohort.Reduced TMT is an independent negative prognostic parameter in patients with progressive glioblastoma and may help to facilitate patient management by supporting patient stratification for therapeutic interventions or clinical trials.
Competition and price among brand-name drugs in the same class: A systematic review of the evidence
Authors: Ameet Sarpatwari, Jonathan DiBello, Marie Zakarian, Mehdi Najafzadeh, Aaron S. Kesselheim
Journal: PLoS Medicine (2019)

Background Some experts have proposed combating rising drug prices by promoting brand–brand competition, a situation that is supposed to arise when multiple US Food and Drug Administration (FDA)-approved brand-name products in the same class are indicated for the same condition. However, numerous reports exist of price increases following the introduction of brand-name competition, suggesting that it may not be effective. We performed a systematic literature review of the peer-reviewed health policy and economics literature to better understand the interplay between new drug entry and intraclass drug prices. Methods and findings We searched PubMed and EconLit for original studies on brand–brand competition in the US market published in English between January 1990 and April 2019. We performed a qualitative synthesis of each study's data, recording its primary objective, methodology, and results. We found 10 empirical investigations, with 1 study each on antihypertensives, anti-infectives, central nervous system stimulants for attention deficit/hyperactivity disorder, disease-modifying therapies for multiple sclerosis, histamine-2 (H2) blockers, and tumor necrosis factor (TNF) inhibitors; 2 studies on cancer medications; and 2 studies on all marketed or new drugs. None of the studies reported that brand–brand competition lowers list prices of existing drugs within a class. The findings of 2 studies suggest that such competition may help restrain how new drug prices are set. Other studies found evidence that brand–brand competition was mediated by the relative quality of competing drugs and the extent to which they are marketed, with safer or more effective new drugs and greater marketing associated with higher intraclass list prices. Our investigation was limited by the studies' use of list rather than net prices and the age of some of the data. Conclusions Our findings suggest that policies to promote brand–brand competition in the US pharmaceutical market, such as accelerating approval of non-first-in-class drugs, will likely not result in lower drug list prices absent additional structural reforms.
YES1 Is a Targetable Oncogene in Cancers Harboring <i>YES1</i> Gene Amplification
Authors: Natsuki Hamanaka, Yoshito Nakanishi, Takakazu Mizuno, Kana Horiguchi-Takei, Nukinori Akiyama, Hiromi Tanimura, Masami Hasegawa, Yasuko Satoh, Yukako Tachibana, Toshihiko Fujii, Kiyoaki Sakata, Kiyomoto Ogasawara, Hirosato Ebiike, Hiroshi Koyano, Haruhiko Sato, Nobuya Ishii, Toshiyuki Mio
Journal: Cancer Research (2019)

Abstract Targeting genetic alterations of oncogenes by molecular-targeted agents (MTA) is an effective approach for treating cancer. However, there are still no clinical MTA options for many cancers, including esophageal cancer. We used a short hairpin RNA library to screen for a new oncogene in the esophageal cancer cell line KYSE70 and identified YES proto-oncogene 1 (YES1) as having a significant impact on tumor growth. An analysis of clinical samples showed that YES1 gene amplification existed not only in esophageal cancer but also in lung, head and neck, bladder, and other cancers, indicating that YES1 would be an attractive target for a cancer drug. Because there is no effective YES1 inhibitor so far, we generated a YES1 kinase inhibitor, CH6953755. YES1 kinase inhibition by CH6953755 led to antitumor activity against YES1-amplified cancers in vitro and in vivo. Yes-associated protein 1 (YAP1) played a role downstream of YES1 and contributed to the growth of YES1-amplified cancers. YES1 regulated YAP1 transcription activity by controlling its nuclear translocation and serine phosphorylation. These findings indicate that the regulation of YAP1 by YES1 plays an important role in YES1-amplified cancers and that CH6953755 has therapeutic potential in such cancers. Significance: These findings identify the SRC family kinase YES1 as a targetable oncogene in esophageal cancer and describe a new inhibitor for YES1 that has potential for clinical utility. See related commentary by Rai, p. 5702
Inherited genetic susceptibility to acute lymphoblastic leukemia in Down syndrome
Authors: Austin L. Brown, Adam J. de Smith, Vincent U. Gant, Wenjian Yang, Michael E. Scheurer, Kyle M. Walsh, Jonathan M. Chernus, Noah A. Kallsen, Shanna A. Peyton, Gareth E. Davies, Erik A. Ehli, Naomi Winick, Nyla A. Heerema, Andrew J. Carroll, Michael J. Borowitz, Brent L. Wood, William L. Carroll, Elizabeth A. Raetz, Eleanor Feingold, Meenakshi Devidas, Lisa F. Barcellos, Helen M. Hansen, Libby Morimoto, Alice Y. Kang, Ivan Smirnov, Jasmine Healy, Caroline Laverdière, Daniel Sinnett, Jeffrey W. Taub, Jillian M. Birch, Pamela Thompson, Logan G. Spector, Maria S. Pombo-de-Oliveira, Andrew T. DeWan, Charles G. Mullighan, Stephen P. Hunger, Ching-Hon Pui, Mignon L. Loh, Michael E. Zwick, Catherine Metayer, Xiaomei Ma, Beth A. Mueller, Stephanie L. Sherman, Joseph L. Wiemels, Mary V. Relling, Jun J. Yang, Philip J. Lupo, Karen R. Rabin
Journal: Blood (2019)
Fractures While Walking Leashed Dogs
Authors: E. Michael Lewiecki
Journal: JAMA Surgery (2019)

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Prognostic role of MET expression in early stage NSCLC.
Authors: Tom John, Carmel Murone, Khashayar Asadi, Adrienne Morey, Simon Knight, Paul Mitchell
Journal: Journal of Clinical Oncology (2013)

7567 Background: The MET receptor tyrosine kinase and its ligand are associated with the malignant phenotype. In non-small cell lung cancer (NSCLC) MET expression increases with disease stage and is involved in de novo and acquired resistance to tyrosine kinase inhibitors. Despite this, in early stage NSCLC small data series have failed to demonstrate MET expression to be prognostic. We investigated a large cohort of patients who underwent curative surgical resection at our institution to determine whether MET receptor or gene amplification was prognostic. Methods: Tissue Microarrays (TMAs) were constructed using 1mm cores of FFPE primary NSCLC tissues in triplicate. TMAs were stained with the SP44 clone (Novus Biologicals) and a H-score calculated based on % cells stained and intensity; (%cellsx1)+(%cellsx2)+(%cellsx3) with a minimum of 0 and maximum of 300. The mean of triplicate values was calculated. MET gene amplification was detected using Ventana’s MET DNP probe with ultraView SISH DNP silver detection, performed on Ventana’s XT autostainer. DNA was isolated and subjected to mutational profiling using Sequenom’s LungCarta panel. Results: Data for 508 patients, 352 (69%) male, were available for analysis including 329 pathological node negative (pN0), 67 pN1, 104 pN2 and 8 patients with resected primaries and solitary brain metastases (M1). Most patients were smokers with only 33 (6%) non-smokers. The median MET H-score was 100 and consistent across N0, N1 and N2 patients, although was higher in M1 patients. Median H-scores were significantly higher in adenocarcinoma compared to squamous cell carcinoma (140 vs 91.5, p&lt;0.0001). Increased MET expression (H-score&gt;100) was seen in 227 (45%) patients and associated with significantly improved overall survival (HR 1.28 95% CI 1.04-1.59; p=0.023). In univariate analyses improved survival occurred in all stages and histologies. DNA and multivariate analyses are pending. MET gene copy number amplification was detected in 11 cases. Conclusions: In contradistinction to advanced NSCLC, increased MET receptor expression is associated with improved survival in a large cohort of early stage lung cancer. Further correlation with mutation status and gene rearrangements will be reported.
Control of Thyroglobulin Synthesis and Secretion
Authors: André J. Van Herle, Gilbert Vassart, Jacques E. Dumont
Journal: New England Journal of Medicine (1979)

(First of Two Parts)THE thyroid has two main endocrine functions: secretion of the thyroid hormones thyroxine (T4) and triiodothyronine (T3) by the follicular cells and secretion of calcitonin by the C cells. Thyroid hormones are first synthesized as a prohormone, thyroglobulin, which is a large glycoprotein. This prohormone is also released by the thyroid and constitutes a normal plasma component. This article reviews recent developments in the synthesis, secretion and control of thyroglobulin. Wherever possible, we discuss data on the human thyroid gland and the clinical aspects of thyroglobulin secretion.Physiologic Features or the Thyroid . . .
Incidence and prognostic impact of KRAS and BRAF mutations in patients undergoing liver surgery for colorectal metastases.
Authors: Georgios Karagkounis, Michael S. Torbenson, Hubert D Daniel, Nilofer Saba Azad, Luis A. Diaz, Ross C. Donehower, Kenzo Hirose, Timothy M. Pawlik, Michael A. Choti
Journal: Journal of Clinical Oncology (2012)

3616 Background: Molecular biomarkers offer the potential for refining prognostic determinants in patients undergoing cancer surgery. Among patients with colorectal cancer metastases, KRAS and BRAF are important biomarkers, but their role in patients undergoing surgical therapy for liver metastases is unknown. In this study, the prevalence and prognostic significance of KRAS and BRAF mutations were determined in patients undergoing surgical therapy of colorectal liver metastases (CRLM). Methods: KRAS and BRAF analysis was performed on 202 patients undergoing curative intent surgical therapy of CRLM between 2003 and 2008. Tumor samples were analyzed for somatic mutations using sequencing analysis (KRAS: codon 12/13, BRAF: V600E). The frequency of mutations was ascertained and their impact on outcome determined relative to other clinicopathologic factors. Results: KRAS gene mutations were detected in 58/202 patients (29%) undergoing surgery for CRLM, comparable to that reported in non-surgical patient series. In contrast, mutation in the BRAF gene was identified in very low frequency in this surgical cohort, found in only 4/202 (2%) patients. KRAS mutations were associated with worse long-term survival (HR=2.13, CI=1.25-3.65), as well as risk of recurrence (HR=1.89, CI=1.12-3.19). ). In addition, KRAS mutation was also associated with risk of recurrence following surgical therapy (HR=1.89, CI=1.12-3.19).While other clinicopathologic features, including tumor number, CEA and primary stage were also associated with survival, KRAS status remained independently predictive of outcome. The low incidence of BRAF mutation limited the ability to determine its prognostic impact. Conclusions: While KRAS mutations were found in approximately one third of patients, BRAF mutations were found in only 2% of patients undergoing surgery for CRLM. KRAS status was an independent predictor of overall and disease-free survival. Molecular biomarkers such as KRAS may help to refine our prognostic assessment of patients undergoing surgical therapy for CRLM.
Feasibility and short-term efficacy of four facio-cervical fields’ conformal radiotherapy for nasopharyngeal carcinoma.
Authors: Wang fang Zheng, Fu Zhenfu
Journal: Journal of Clinical Oncology (2012)

5568 Background: Conventional bilateral facio-cervical fields increased the local control and overall rates for nasopharyngeal carcinoma, and generated severe late complications, while intensity-modulated radiation therapy (IMRT) may take up a lot of labor power and material resources.This study was to explore feasibility and short-term efficacy of four facio-cervical fields’ conformal radiotherapy (4F-CRT) for nasopharyngeal carcinoma. Methods: Between November 2007 and June 2009, 101 patients with histology-proven nonmetastatic NPC were rolled into this study and received 4F-CRT. 90 of all patients received four cycles chemotherapy. Results: The treatment was completed for all patients within 7 weeks. The complete response (CR) rate was 95.0% (96/101) and the partial response (PR) rate 5.0% (5/101). Overall response was 100% for nasopharyngeal lesions. The CR rate was 90.0% (91/101) and the PR rate 7.0% (7/101) in lymph node lesions. One year local control, regional control, overall survival (OS) rate, metastasis-free survival (MFS) and disease-free survival (DFS) rate are 100%, 100%, 100%, 97%, 97%, respectively. The major toxicities observed were grades 1-2 leukocytopenia. Conclusions: 4F-CRT can generate desirable dose distribution of tumor volume for nasopharyngeal carcinoma. The short-term efficacy of 4F-CRT is satisfactory and its acute toxicities are tolerable.
Efficacy of tumor treatment field (TTF) therapy alone and in combination with chemotherapyin pancreatic cancer preclinical models.
Authors: Moshe Giladi, Rosa S. Schneiderman, Yaara Porat, Aviran Itzhaki, Daniel Mordechovich, Uri Weinberg, Yoram Palti
Journal: Journal of Clinical Oncology (2012)

e14616 Background: TTF therapy is a novel, non-invasive treatment modality for solid tumors and was recently approved by the FDA for recurrent glioblastoma. It utilizes alternating electric fields to inhibit tumor growth, by mitotic spindle disruption and destruction of plasma membrane integrity during cytokinesis. TTF inhibits the growth of many solid tumor cell lines in vitro and in vivo. The optimal treatment for pancreas cancer remains elusive, thus we sought to evaluate the efficacy of TTF in pre-clinical pancreatic cancer models. Methods: Cultures of hamster and human pancreatic adenocarcinoma cell lines (PC1-0 and AsPC-1, respectively) were treated with TTF (frequencies ranging from 75 to 300 kHz), using two pairs of perpendicularly oriented insulated transducer arrays. Once determining optimal frequency, TTF was combined with chemotherapy (gemcitabine or 5-Fluorouracil, 5-FU). Hamsters bearing syngeneic, orthotopic pancreatic tumors were treated with either TTF alone or in combination with gemcitabine or 5-FU. Results: TTF treatment had significant inhibitory effect on proliferation of pancreatic cancer cultures. The maximal inhibitory effect for PC1-0 and ASPC-1 was observed when TTF frequencies of 100 and 150 kHz were applied (respectively). The application of TTF to cultures treated with either gemcitabine or 5-FU resulted in an additive inhibitory effect. In-vivo, TTF therapy, either alone or in combination with chemotherapy, resulted in a significant decrease in tumor weight and volume. Compared to chemotherapy alone, TTF increased tumor response to both gemcitabine and 5-FU. Histological analysis demonstrated higher mitotic index in TTF-treated tumors, consistent with the mitotic arrest previously shown in TTF treated cultures. Conclusions: TTF therapy demonstrated efficacy in pancreatic adenocarcinoma in both in vitro and in vivo models. These results support the evaluation of this novel treatment modality in combination with standard chemotherapy in pancreatic cancer patients. A pilot study is in development to test the clinical benefit of combined TTF and gemcitabine in patients with advanced pancreatic adenocarcinoma.
Novel technique for intraductal cholangioscopy-assisted biliary drainage with over-the-wire microcatheter manipulation
Authors: Michihiro Yoshida, Akihisa Kato, Kazuki Hayashi, Itaru Naitoh, Katsuyuki Miyabe, Yasuki Hori, Go Asano
Journal: Endoscopy (2019)

Cholangioscopy-assisted guidewire placement is reported to be a useful method for endoscopic biliary drainage that is made difficult by complex strictures and obstructions [1] [2] [3] [4] [5]. However, the guidewire sometimes becomes misdirected because of the lack of contrast-filled images. With the aim of improving safety and certainty, we present two practical cases that employ a novel technique using an over-the-wire microcatheter through digital intraductal cholangioscopy (IDC) (SpyGlass DS; Boston Scientific, Natick, Massachusetts, USA).