tbuckley/cabot-search huggingface dataset:
Peroral endoscopic myotomy: a meta-analysis
Authors: Emmanuel Akintoye, Nitin Kumar, Itegbemie Obaitan, Quazim Alayo, Christopher Thompson
Journal: Endoscopy (2016)

<b>Background and study aim: </b>Peroral endoscopic myotomy (POEM) is a relatively novel minimally invasive technique that is used to treat achalasia and other esophageal motility disorders. We systematically reviewed the medical literature in order to evaluate the safety and efficacy of POEM. <b>Methods: </b>We performed a comprehensive review and meta-analysis of studies published up to March 2016 that reported on clinical outcomes of POEM. Five databases were searched: MEDLINE, EMBASE, Ovid, CINAHL, and Cochrane. <b>Results:</b> A total of 36 studies involving 2373 patients were included in the review. Clinical success (Eckardt score ≤ 3) was achieved in 98 % (95 % confidence interval [CI] 97 % – 100 %) of patients after the procedure. The mean Eckardt score decreased from 6.9 ± 0.15 preoperatively to 0.77 ± 0.10, 1.0 ± 0.10, and 1.0 ± 0.08 within 1, 6, and 12 months of treatment. In addition, there were significant decreases in the average lower esophageal sphincter pressure, integrated relaxation pressure, and the average heights of the barium column following a timed barium esophagogram after the procedure. After a mean follow-up of 8 months post-procedure, the rates of symptomatic gastroesophageal reflux, esophagitis on esophagogastroduodenoscopy, and abnormal acid exposure were 8.5 % (95 %CI 4.9 % – 13 %), 13 % (95 %CI 5.0 % – 23 %), and 47 % (95 %CI 21 % – 74 %), respectively. <b>Conclusions: </b>POEM appears to be safe and effective based on the large body of current evidence, and warrants consideration as first-line therapy when an expert operator is available.
Robotic and Open Radical Prostatectomy: The First Prospective Randomised Controlled Trial Fuels Debate Rather than Closing the Question
Authors: Nicola Fossati, Peter Wiklund, Charles-Henry Rochat, Francesco Montorsi, Prokar Dasgupta, Rafael Sanchez-Salas, Abdullah E. Canda, Thierry Piechaud, Walter Artibani, Alexandre Mottrie
Journal: European Urology (2016)
Simplified Monitoring of CD4 T-Cell Receptor Repertoire Provides Effective Management Strategies in the Patients with Persistent or Recurrent Graft-Versus-Host Disease
Authors: Rie Kuroda, Shintaro Mase, Hideaki Maeba, Raita Araki, Yasuhiro Ikawa, Toshihiro Fujiki, Masaki Fukuda, Shoichi Koizumi, Akihiro Yachie, Ryosei Nishimura
Journal: Blood (2014)
Abstract 5290: Identification of novel prognostic genes associated with risk of recurrence in early breast cancer patients
Authors: Mi Jeong Kwon
Journal: Cancer Research (2015)

Abstract Introduction : In order to determine the need for adjuvant chemotherapy in early estrogen receptor-positive breast cancer, especially luminal A, it is important to identify patients at high risk of recurrence. This study was performed to identify novel prognostic genes associated with the recurrence risk of patients with lymph node-negative luminal A (LN−/LumA) breast cancer. Methods : RNA was extracted from formalin-fixed, paraffin-embedded (FFPE) breast cancer tissues. The expression levels of 16 candidate genes identified from our previous study were measured using quantitative real-time reverse transcription-PCR in 926 FFPE samples. We used Cox proportional hazards models to assess the prognostic value of clinical and gene variables for recurrence. Results : Of the 796 patients with recurrence-free survival (RFS) and 826 patients with overall survival (OS), 24.4% (194/796) and 24.0% (198/826), respectively, had LN−/LumA breast cancer. Univariate analysis showed that clinical variables such as tumor size, involvement of lymph nodes, and tumor stage were not significantly associated with RFS and OS of patients with this subtype. In contrast, there was a significant association between gene expression and patient outcomes. Higher expression of 4 proliferation-related genes (F4, M4, R3, and U4) was significantly correlated with shorter OS and RFS. Importantly, in multivariate analyses, high expression of R3 and U4 remained significantly associated with RFS. While not significantly related to RFS in univariate analysis, immune response-related B5 expression had a significantly lower harzard ratio in the multivariate analysis (P = 0.004), indicating it was an independent positive prognostic factor. Higher expression of M4 (P = 0.014) and R3 (P = 0.01) was independently associated with shorter OS. When tested using gene variables, prognostic models for risk of recurrence included M4, R3, U4, and B5. Moreover, patients with low B5 and high U4 expressions had a significantly shorter RFS than those with high B5 and low U4 expressions. Conclusions : Novel prognostic genes identified in our study give more significant information on the risk of recurrence than clinical variables in patients with LN−/LumA breast cancer. Multigene expression signatures, including immune response-related genes, can be used to identify patients at high risk of recurrence in this subtype of breast cancer. Citation Format: Mi Jeong Kwon. Identification of novel prognostic genes associated with risk of recurrence in early breast cancer patients. [abstract]. In: Proceedings of the 106th Annual Meeting of the American Association for Cancer Research; 2015 Apr 18-22; Philadelphia, PA. Philadelphia (PA): AACR; Cancer Res 2015;75(15 Suppl):Abstract nr 5290. doi:10.1158/1538-7445.AM2015-5290
A New Concept of Enhancing Immuno-Chemotherapeutic Effects Against B16F10 Tumor <i>via</i> Systemic Administration by Taking Advantages of the Limitation of EPR Effect
Authors: Yuting Yang, Xiaowei Tai, Kairong Shi, Shaobo Ruan, Yue Qiu, Zhirong Zhang, Bing Xiang, Qin He
Journal: Theranostics (2016)

The enhanced permeability and retention (EPR) effect has been comfortably accepted, and extensively assumed as a keystone in the research on tumor-targeted drug delivery system. Due to the unsatisfied tumor-targeting efficiency of EPR effect being one conspicuous drawback, nanocarriers that merely relying on EPR effect are difficult to access the tumor tissue and consequently trigger efficient tumor therapy in clinic. In the present contribution, we break up the shackles of EPR effect on nanocarriers thanks to their universal distribution characteristic. We successfully design a paclitaxel (PTX) and alpha-galactosylceramide (αGC) co-loaded TH peptide (AGYLLGHINLHHLAHL(Aib)HHIL-Cys) -modified liposome (PTX/αGC-TH-Lip) and introduce a new concept of immuno-chemotherapy combination via accumulation of these liposomes at both spleen and tumor sites naturally and simultaneously. The PTX-initiated cytotoxicity attacks tumor cells at tumor sites, meanwhile, the αGC-triggered antitumor immune response emerges at spleen tissue. Different to the case that liposomes are loaded with sole drug, in this concept two therapeutic processes effectively reinforce each other, thereby elevating the tumor therapy efficiency significantly. The data demonstrates that the PTX/αGC-TH-Lip not only possess therapeutic effect against highly malignant B16F10 melanoma tumor, but also adjust the in vivo immune status and induce a more remarkable systemic antitumor immunity that could further suppress the growth of tumor at distant site. This work exhibits the capability of the PTX/αGC-TH-Lip in improving immune-chemotherapy against tumor after systemic administration.
Sentinel Node Procedure in Prostate Cancer: A Systematic Review to Assess Diagnostic Accuracy
Authors: Esther M.K. Wit, Cenk Acar, Nikolaos Grivas, Cathy Yuan, Simon Horenblas, Fredrik Liedberg, Renato A. Valdes Olmos, Fijs W.B. van Leeuwen, Nynke S. van den Berg, Alexander Winter, Friedhelm Wawroschek, Stephan Hruby, Günter Janetschek, Sergi Vidal-Sicart, Steven MacLennan, Thomas B. Lam, Henk G. van der Poel
Journal: European Urology (2016)
The cystic fibrosis transmembrane conductance regulator controls biliary epithelial inflammation and permeability by regulating Src tyrosine kinase activity
Authors: Romina Fiorotto, Ambra Villani, Antonis Kourtidis, Roberto Scirpo, Mariangela Amenduni, Peter J. Geibel, Massimiliano Cadamuro, Carlo Spirli, Panos Z. Anastasiadis, Mario Strazzabosco
Journal: Hepatology (2016)

In the liver, the cystic fibrosis (CF) transmembrane conductance regulator (CFTR) regulates bile secretion and other functions at the apical membrane of biliary epithelial cells (i.e., cholangiocytes). CF‐related liver disease is a major cause of death in patients with CF. CFTR dysfunction affects innate immune pathways, generating a para‐inflammatory status in the liver and other epithelia. This study investigates the mechanisms linking CFTR to toll‐like receptor 4 activity. We found that CFTR is associated with a multiprotein complex at the apical membrane of normal mouse cholangiocytes, with proteins that negatively control Rous sarcoma oncogene cellular homolog (Src) activity. In CFTR‐defective cholangiocytes, Src tyrosine kinase self‐activates and phosphorylates toll‐like receptor 4, resulting in activation of nuclear factor kappa‐light‐chain‐enhancer of activated B cells and increased proinflammatory cytokine production in response to endotoxins. This Src/nuclear factor kappa‐light‐chain‐enhancer of activated B cells‐dependent inflammatory process attracts inflammatory cells but also generates changes in the apical junctional complex and loss of epithelial barrier function. Inhibition of Src decreased the inflammatory response of CF cholangiocytes to lipopolysaccharide, rescued the junctional defect in vitro , and significantly attenuated endotoxin‐induced biliary damage and inflammation in vivo (Cftr knockout mice). Conclusion : These findings reveal a novel function of CFTR as a regulator of toll‐like receptor 4 responses and cell polarity in biliary epithelial cells; this mechanism is pathogenetic, as shown by the protective effects of Src inhibition in vivo , and may be a novel therapeutic target in CF‐related liver disease and other inflammatory cholangiopathies. (H epatology 2016;64:2118‐2134).
Endothelial nitric oxide synthase augments anthracycline-induced cardiac injury
Authors: G Neilan, DS Jassal, ES Buys, MJ Raher, F Ichinose, TM Perez-Sanz, DB Bayne, A Graveline, Stefan Janssens, MH Picard, M Scherrer-Crosbie, KD Bloch
Journal: Circulation (2005)
All Oral Sofosbuvir-Based Antiviral Therapy in Liver Transplant Recipients Affected by Moderate-Severe Hepatitis C Recurrence: Predictors of Viral Response and Survival
Authors: S. Martini, D. Arese, M. Sacco, S. Strona, D. Cocchis, S. Mirabella, G. Rizza, A. Ottobrelli, M.R. Torrani-Cerenzia, F. Balzola, P. Magistroni, P. Moschini, A. Amoroso, M. Salizzoni, M. Rizzetto, G.M. Saracco, R. Romagnoli
Journal: Journal of Hepatology (2016)
Feasibility of Extracted-Overlay Fusion Imaging for Intraoperative Treatment Evaluation of Radiofrequency Ablation for Hepatocellular Carcinoma
Authors: Yuki Makino, Yasuharu Imai, Takumi Igura, Sachiyo Kogita, Yoshiyuki Sawai, Kazuto Fukuda, Takayuki Iwamoto, Junya Okabe, Manabu Takamura, Norihiko Fujita, Masatoshi Hori, Tetsuo Takehara, Masatoshi Kudo, Takamichi Murakami
Journal: Liver Cancer (2016)

&lt;b&gt;&lt;i&gt;Background and Aims: &lt;/i&gt;&lt;/b&gt;Extracted-overlay fusion imaging is a novel computed tomography/magnetic resonance-ultrasonography (CT/MR-US) imaging technique in which a target tumor with a virtual ablative margin is extracted from CT/MR volume data and synchronously overlaid on US images. We investigated the applicability of the technique to intraoperative evaluation of radiofrequency ablation (RFA) for hepatocellular carcinoma (HCC). &lt;b&gt;&lt;i&gt;Methods: &lt;/i&gt;&lt;/b&gt;This retrospective study analyzed 85 HCCs treated with RFA using extracted-overlay fusion imaging for guidance and evaluation. To perform RFA, an electrode was inserted targeting the tumor and a virtual 5-mm ablative margin overlaid on the US image. Following ablation, contrast-enhanced US (CEUS) was performed to assess the ablative margin, and the minimal ablative margins were categorized into three groups: (I) margin &lt;0 mm (protrusion), (II) margin 0 to &lt;5 mm, and (III) margin ≥5 mm. Margin assessment was based on the positional relationship between the overlaid tumor plus margin and the perfusion defect of the ablation zone. Tumors in group I underwent repeat ablation until they were in groups II or III. The final classifications were compared with those obtained by retrospectively created fusion images of pre- and post-RFA CT or MR imaging (CT-CT/MR-MR fusion imaging). &lt;b&gt;&lt;i&gt;Results: &lt;/i&gt;&lt;/b&gt;Treatment evaluation was impossible using CEUS in six HCCs because the tumors were located far below the body surface. Of the remaining 79 HCCs, the categorizations of minimal ablative margins between CEUS extracted-overlay fusion imaging and CT-CT/MR-MR fusion imaging were in agreement for 72 tumors (91.1%) (Cohen's quadratic-weighted kappa coefficient 0.66, good agreement, p&lt;0.01). &lt;b&gt;&lt;i&gt;Conclusions: &lt;/i&gt;&lt;/b&gt;Extracted-overlay fusion imaging combined with CEUS is feasible for the evaluation of RFA and enables intraoperative treatment evaluation without the need to perform contrast-enhanced CT.
To follow up or not? A new model of supportive care for early breast cancer.
Authors: J. Dent, A. Topping, C. Ferguson, J. Stephenson, M. McCoy, V. Allinson, S. Brayford
Journal: Journal of Clinical Oncology (2011)

9098 Background: Routine follow-up after curative treatment for early breast cancer exists to monitor for local recurrence and provide support for patients. Hospital visits can be stressful for patients and evidence indicates most recurrences are first identified by the patient. The value of resource-intense clinical follow-up is constantly being questioned. Many believe that time spent seeing essentially well-women is not clinically beneficial or an efficient use of time. Methods: This pilot study tested the feasibility and acceptability of a new supportive model of follow-up using quality-of-life (QOL) questionnaires plus qualitative diary evaluations. All patients attended four half day patient education workshops with course evaluations, followed by randomised to open access (OA) or hospital follow up (HFU). QOL including Hospital Anxiety and Depression Score (HADS), EORTC QLQ-C30 and BR23 were performed at baseline and 6 months, with further results awaited for 12, 18 and 24 months. Results: 106 women were recruited to the pilot study. 53 were randomised to HFU and 53 to OA. Multivariate analyses of covariance (MANCOVA) tests were conducted on all QOL data. Age was included as a covariate. Follow-up ANCOVAs on individual function and symptom outcomes were also conducted. The MANCOVA analyses indicated no statistically significant differences in change scores between HFU and OA groups, or between patients of different ages, on any of the three questionnaires. In all cases the effect of group had a greater effect on change (baseline-6 months) scores than the effect of age. Univariate ANCOVA tests and descriptive analyses showed performance improvement in many of the individual function and symptom scales in the OA group. Conclusions: While open access patients showed greater mean improvements in more scales than patients seen in clinic, follow-up method does not appear to significantly affect overall outcomes on any of the three questionnaires. As an influencing factor, the patients' age is less significant than the assigned group. This new model is feasible and acceptable. It is being adopted as standard across the Yorkshire Cancer Network.
Use of whole genome sequencing to identify highly recurrent somatic mutations in Waldenström’s macroglobulinemia.
Authors: Zachary R Hunter, Lian Xu, Guang Yang, Yangsheng Zhou, Xia Liu, Yang Cao, Christina Tripsas, Robert J Manning, Christopher J Patterson, Patricia S Sheehy, Steven P. Treon
Journal: Journal of Clinical Oncology (2012)

8107 Background: Waldenstrom’s Macroglobulinemia (WM) is an IgM secreting lymphoplasmacytic lymphoma. The genetic basis for this disease remains to be clarified. Methods: We performed whole genome sequencing (WGS) using CD19 + selected bone marrow lymphoplasmacytic cells (LPC) from 30 WM patients. For 10 of these patients, paired CD19 + depleted peripheral blood samples were used for WGS as normal controls. Results: The most common somatic variants identified and validated by Sanger sequencing included MYD88 L265P, an activating mutation for IRAK/TRAF6/NFKB and MAPK signaling, which was observed in 27/30 (90%) patients; the N-terminal domain of CXCR4, which included mutations associated with WHIM syndrome and confer constitutive CXCR4 signaling resulting from dysfunctional receptor endocytosis, a finding observed in 8/30 (27%) patients, and ARID1A (5/30; 17%), a tumor suppressor gene. Less common somatic variants were also identified in MUC16 (4/30; 13%), TRAF2 (3/30; 10%), TRRAP (3/30; 10%) and MYBBP1A (2/30; 7%). Conclusions: Using WGS and confirmatory Sanger sequencing, we have identified several somatic variants with oncogenic function, the most common of which include MYD88 L265P, the N-terminal domain of CXCR4, and ARID1A.
Targeting the CXCR4 Pathway: Safety, Tolerability and Clinical Activity of Ulocuplumab (BMS-936564), an Anti-CXCR4 Antibody, in Relapsed/Refractory Acute Myeloid Leukemia
Authors: Pamela S. Becker, James M. Foran, Jessica K. Altman, Abdulraheem Yacoub, Januario E. Castro, Peter Sabbatini, Clifford Dilea, Mark Wade, Guan Xing, Andres Gutierrez, Lewis Cohen, B. Douglas Smith
Journal: Blood (2014)
A comparison of topical levocabastine and oral terfenadine in the treatment of allergic rhinoconjunctivitis
Journal: Allergy (1993)

This study was undertaken to compare the efficacy of twice‐daily levocabastine, a new topical H 1 ‐blocking antihistamine, with that of twice‐daily oral terfenadine in the treatment of allergic rhinoconjunctivitis. A total of 128 adult patients with a history of birch‐pollen‐provoked allergic rhinoconjunctivitis participated in this double‐blind, parallel‐group study. Ocular and nasal symptoms, assessed by a 100‐mm visual analog scale, were recorded daily on diary cards for a period of 8 weeks. Global assessments of treatment efficacy were also performed. Conventional statistical analysis detected no significant differences between the two treatment regimens. Similarly, there was no difference in the number or type of adverse reactions in each treatment group. Statistical analysis according to Hauck &amp; Andersson confirmed equivalence between the two treatment regimens. Topical levocabastine appears to be as effective and well‐tolerated as oral terfenadine in the treatment of allergic rhinoeonjunctivitis. The Livostin Study Group. A comparison of topical levocabastine and oral terfenadine in the treatment of allergic rhinoconjunctivitis.
Optimization of Early Response Monitoring and Prediction of Cancer Antiangiogenesis Therapy via Noninvasive PET Molecular Imaging Strategies of Multifactorial Bioparameters
Authors: Xiao Bao, Ming-Wei Wang, Jian-Min Luo, Si-Yang Wang, Yong-Ping Zhang, Ying-Jian Zhang
Journal: Theranostics (2016)

Objective: Antiangiogenesis therapy (AAT) has provided substantial benefits regarding improved outcomes and survival for suitable patients in clinical settings.Therefore, the early definition of therapeutic effects is urgently needed to guide cancer AAT.We aimed to optimize the early response monitoring and prediction of AAT efficacy, as indicated by the multi-targeted anti-angiogenic drug sunitinib in U87MG tumors, using noninvasive positron emission computed tomography (PET) molecular imaging strategies of multifactorial bioparameters.Methods: U87MG tumor mice were treated via intragastric injections of sunitinib (80 mg/kg) or vehicle for 7 consecutive days.Longitudinal MicroPET/CT scans with 18 F-FDG, 18 F-FMISO, 18 F-ML-10 and 18 F-Alfatide II were acquired to quantitatively measure metabolism, hypoxia, apoptosis and angiogenesis on days 0, 1, 3, 7 and 13 following therapy initiation.Tumor tissues from a dedicated group of mice were collected for immunohistochemical (IHC) analysis of key biomarkers (Glut-1, CA-IX, TUNEL, ανβ3 and CD31) at the time points of PET imaging.The tumor sizes and mouse weights were measured throughout the study.The tumor uptake (ID%/gmax), the ratios of the tumor/muscle (T/M) for each probe, and the tumor growth ratios (TGR) were calculated and used for statistical analyses of the differences and correlations.Results: Sunitinib successfully inhibited U87MG tumor growth with significant differences in the tumor size from day 9 after sunitinib treatment compared with the control group (P < 0.01).The uptakes of 18 F-FMISO (reduced hypoxia), 18 F-ML-10 (increased apoptosis) and 18 F-Alfatide II (decreased angiogenesis) in the tumor lesions significantly changed during the early stage (days 1 to 3) of sunitinib treatment; however, the uptake of 18 F-FDG (increased glucose metabolism) was significantly different during the late stage.The PET imaging data of each probe were all confirmed via ex vivo IHC of the relevant biomarkers.Notably, the PET imaging of 18 F-Alfatide II and 18 F-FMISO was significantly correlated (all P < 0.05) with TGR, whereas the imaging of 18 F-FDG and 18 F-ML-10 was not significantly correlated with TGR. Conclusion:Based on the tumor uptake of the PET probes and their correlations with MVD and TGR, 18 F-Alfatide II PET may not only monitor the early response but also precisely predict the therapeutic efficacy of the multi-targeted, anti-angiogenic drug sunitinib in U87MG tumors.In conclusion, it is feasible to optimize the early response monitoring and efficacy prediction of Ivyspring International
Cost-effectiveness of Intensive Blood Pressure Management
Authors: Ilana B. Richman, Michael Fairley, Mads Emil Jørgensen, Alejandro Schuler, Douglas K. Owens, Jeremy D. Goldhaber-Fiebert
Journal: JAMA Cardiology (2016)

Among high-risk patients with hypertension, targeting a systolic blood pressure of 120 mm Hg reduces cardiovascular morbidity and mortality compared with a higher target. However, intensive blood pressure management incurs additional costs from treatment and from adverse events.To evaluate the incremental cost-effectiveness of intensive blood pressure management compared with standard management.This cost-effectiveness analysis conducted from September 2015 to August 2016 used a Markov cohort model to estimate cost-effectiveness of intensive blood pressure management among 68-year-old high-risk adults with hypertension but not diabetes. We used the Systolic Blood Pressure Intervention Trial (SPRINT) to estimate treatment effects and adverse event rates. We used Centers for Disease Control and Prevention Life Tables to project age- and cause-specific mortality, calibrated to rates reported in SPRINT. We also used population-based observational data to model development of heart failure, myocardial infarction, stroke, and subsequent mortality. Costs were based on published sources, Medicare data, and the National Inpatient Sample.Treatment of hypertension to a systolic blood pressure goal of 120 mm Hg (intensive management) or 140 mm Hg (standard management).Lifetime costs and quality-adjusted life-years (QALYs), discounted at 3% annually.Standard management yielded 9.6 QALYs and accrued $155 261 in lifetime costs, while intensive management yielded 10.5 QALYs and accrued $176 584 in costs. Intensive blood pressure management cost $23 777 per QALY gained. In a sensitivity analysis, serious adverse events would need to occur at 3 times the rate observed in SPRINT and be 3 times more common in the intensive management arm to prefer standard management.Intensive blood pressure management is cost-effective at typical thresholds for value in health care and remains so even with substantially higher adverse event rates.