tbuckley/cabot-search huggingface dataset:
Individual and Population Comparisons of Surgery and Radiotherapy Outcomes in Prostate Cancer Using Bayesian Multistate Models
Authors: Lauren J. Beesley, Todd M. Morgan, Daniel E. Spratt, Udit Singhal, Felix Y. Feng, Allison Cullen Furgal, William C. Jackson, Stephanie Daignault, Jeremy M. G. Taylor
Journal: JAMA Network Open (2019)

Whether surgery or radiotherapy is the preferred treatment for patients with localized prostate cancer continues to be debated, and randomized clinical trials cannot yet fully address this question. Furthermore, there may be heterogeneity in responses, and the optimal treatment for a patient will depend on his clinical and tumor characteristics.To use a unified statistical approach to compare the association of surgery and radiotherapy with both metastatic clinical failure (CF) and survival in localized prostate cancer and to develop an online calculator for individualized, treatment-specific outcome prediction.Cohort study for statistical analysis and development of individualized predictions using Bayesian multistate models that jointly consider both CF and survival and adjust for confounding factors. This study used data from patients treated at the University of Michigan between January 1, 1996, and July 1, 2013, with detailed information on treatment, patient and tumor characteristics, and outcomes. Primary analyses were performed in 2017 and 2018. Participants were a cohort of 4544 patients with localized prostate cancer undergoing primary treatment.Radical prostatectomy and external beam radiotherapy.The clinical outcomes were metastatic CF, death after CF, and death from other causes. The adjustment factors were age, prostate gland volume, prostate-specific antigen level, comorbidities, Gleason score, perineural invasion, cT category, race, and treatment year. An online calculator was developed to estimate risks for multiple outcomes for any patient based on 2 treatment choices and on his clinical and tumor characteristics.Among 4544 men (mean [SD] age, 61.2 [8.0] years), 3769 underwent radical prostatectomy, 775 received external beam radiotherapy, 157 (3.5%) had CF, 90 (2.0%) died after CF, and 378 (8.3%) died of other causes. Across all patients, there was no significant difference in risk of CF for surgery vs radiotherapy (hazard ratio, 0.80; 95% CI, 0.52-1.23). However, using multistate models, in some cases individualized predictions resulted in different expected outcomes between surgery and radiotherapy for a given patient.In this study, after adjustment for measured confounders, the hazard of CF was similar between treatments on average. However, these data indicate a greater oncologic benefit for some individual patients if treated with surgery and for other patients if treated with radiotherapy. Individualized predictions provide a novel approach to facilitate treatment decision making.
A murine model of diarrhea, growth impairment and metabolic disturbances with<i>Shigella flexneri</i>infection and the role of zinc deficiency
Authors: Pedro Henrique Q.S. Medeiros, Solanka E. Ledwaba, David T. Bolick, Natasa Giallourou, Lauren K. Yum, Deiziane V.S. Costa, Reinaldo B. Oriá, Eileen M. Barry, Jonathan R. Swann, Aldo Ângelo M. Lima, Hervé Agaisse, Richard L. Guerrant
Journal: Gut Microbes (2019)

Shigella is one of the major enteric pathogens worldwide. We present a murine model of S. flexneri infection and investigate the role of zinc deficiency (ZD). C57BL/6 mice fed either standard chow (HC) or ZD diets were pretreated with an antibiotic cocktail and received S. flexneri strain 2457T orally. Antibiotic pre-treated ZD mice showed higher S. flexneri colonization than non-treated mice. ZD mice showed persistent colonization for at least 50 days post-infection (pi). S. flexneri-infected mice showed significant weight loss, diarrhea and increased levels of fecal MPO and LCN in both HC and ZD fed mice. S. flexneri preferentially colonized the colon, caused epithelial disruption and inflammatory cell infiltrate, and promoted cytokine production which correlated with weight loss and histopathological changes. Infection with S. flexneri ΔmxiG (critical for type 3 secretion system) did not cause weight loss or diarrhea, and had decreased stool shedding duration and tissue burden. Several biochemical changes related to energy, inflammation and gut-microbial metabolism were observed. Zinc supplementation increased weight gains and reduced intestinal inflammation and stool shedding in ZD infected mice. In conclusion, young antibiotic-treated mice provide a new model of oral S. flexneri infection, with ZD promoting prolonged infection outcomes.
Laparoscopic versus open adhesiolysis for adhesive small bowel obstruction (LASSO): an international, multicentre, randomised, open-label trial
Authors: Ville Sallinen, Salomone Di Saverio, Eija Haukijärvi, Risto Juusela, Heidi Wikström, Vesa Koivukangas, Fausto Catena, Berndt Enholm, Arianna Birindelli, Ari Leppäniemi, Panu Mentula
Journal: The Lancet. Gastroenterology & hepatology (2019)
Abstract 12797: Morphology and Type of Repair of the Atrioventricular Valve in Patients With Single Ventricle Undergoing Staged Palliation
Authors: Masamichi Ono, Melchior Burri, Julie Cleuziou, Jelena Pabst von Ohain, Elisabeth Beran, Alfred Hager, Christian Schreiber, Rüdiger Lange
Journal: Circulation (2016)

Introduction: Significant atrioventricular valve (AVV) regurgitation is a known predictor of adverse outcomes after the Fontan procedure. AVV morphology in single ventricle can be complex and the underlying mechanisms of AVV regurgitation are multifactorial. Hypothesis: We analyzed our experience with AVV repair in patients with single ventricle, focusing on the mechanisms of AVV regurgitation and repeat AVV surgery. Methods: Among 460 patients undergoing total cavopulmonary connection (TCPC), 81 (18%) had at least one AVV repair prior or at TCPC. Morphology and function of AVV, ventricular type, and prior palliative surgery were analyzed in all patients in order to identify the risk factors for AVV repair, redo AVV surgery, and AVV replacement. Results: AVV morphology was two separated AVV in 24 patients (30%), mitral in 5 (6%), tricuspid in 36 (44%), and common AVV in 16 (20%). The initial AVV repair was performed at a median age of 2.0 [0.9-4.0] years. AVV regurgitation was due to one or more of the following mechanism: dysplastic leaflet in 45 patients (56%), leaflet prolapse in 42 (52%), cleft in 19 (24%), and chordal anomaly in 11 (14%). These structural anomalies were observed in 69 patients (85%), and two or more anomalies were involved in 49 patients (61%). Pure annular dilation was observed in 12 patients (15%). A second surgery was necessary in 30 patients (37%) and a third in 5 (6%). The initial repair was needed earlier in patients with a leaflet prolapse (p=0.01). Repeat repair was frequently needed in patients with high degree of AVV regurgitation prior to initial surgery (p=0.02) and common AVV (p=0.002). AVV replacement was frequently needed in patients with chordal anomalies (p=0.002) and two or more anomalies (p=0.001). Conclusions: In the majority of the patients, structural anomalies of the AVV lead to regurgitation, and cause early need of initial repair, of repeat surgery, and of AVV replacement. High degree of AVV regurgitation prior to initial AVV repair was a risk factor for repeat surgery.
How do advanced diagnostics support public health policy development?
Authors: Jacob Moran-Gilad
Journal: Eurosurveillance (2019)

Preview this article: How do advanced diagnostics support public health policy development?, Page 1 of 1 < Previous page | Next page > /docserver/preview/fulltext/eurosurveillance/24/4/eurosurv-24-4-1-1.gif
Clinical and Genetic Characteristics of Patients with Shwachman-Diamond Syndrome in Japan
Authors: Kenichiro Watanabe, Hirokazu Kanegane, Takayuki Hamabata, Kagehiro Kozuki, Katsutsugu Umeda, Hiroo Ueno, Kenichi Yoshida, Asahito Hama, Yusuke Okuno, Hideki Muramatsu, Yoshiyuki Takahashi, Daisuke Hasegawa, Atsushi Manabe, Akira Ohara, Masafumi Ito, Seishi Ogawa, Seiji Kojima, Etsuro Ito
Journal: Blood (2018)
Imatinib Protects Against Hypoxia/Reoxygenation Induced Lung and Kidney Injury in a Humanized Mouse Model for SCD
Authors: Alessandro Mattè, Enrica Federti, Antonio Rechiutti, Amtonella Panataleo, Roberta Russo, Francesco Turrini, Angela Siciliano, Pierre Louis Tharaux, Wassim El Nemer, Serge Cedrick, Anne Janin, Christophe Leboeuf, Wilson Babu, Achille Iolascon, Carlo Brugnara, Lucia De Franceschi
Journal: Blood (2018)
Phase II randomized, double-blind study of mFOLFIRINOX plus ramucirumab versus mFOLFIRINOX plus placebo in advanced pancreatic cancer patients (HCRN GI14-198).
Authors: Walid Labib Shaib, Manali Rupji, Tina Ashley Khair, Erwin L. Robin, Bassel F. El-Rayes, Timothy K. Huyck, Yuan Liu, Mohamad Bassam Sonbol, Tanios S. Bekaii-Saab
Journal: Journal of Clinical Oncology (2021)

413 Background: Vascular endothelial growth factor (VEGF) and VEGF receptor (VEGFR)-mediated signaling and angiogenesis contribute to the pathogenesis and progression of pancreatic adenocarcinoma (PCA).VEGF is expressed in all PCA tumors. VEGF-A/VEGFR-2 signaling plays an important role in inducing invasion and migration of PCA cells. The pVEGFR-2 is significantly associated with invasion of the anterior capsule of pancreas and arteries. In preclinical studies, the anti-tumor activity of fluoropyrimidines, but not that of gemcitabine, caused the release of bone marrow derived circulating endothelial progenitor cells (CEPs) and Tie-2 expressing monocytes (TEMs) as well as the induction of pro-angiogenic growth factors. Methods: This phase II randomized, multi-center, and double-blinded trial was designed to compare the efficacy and safety of mFOLFIRINOX/ramucirumab (Arm A) versus mFOLFIRINOX/ placebo (Arm B) as front-line therapy in recurrent or metastatic PCA patients. The primary endpoint was progression free survival (PFS) at 9 months, and the secondary endpoints included overall survival (OS) and response rate. Results: A total of 86 subjects were enrolled, 82 were eligible (42 in Arm A v. 40 in Arm B). The mean age of the subjects in the two arms were comparable (61.7 v. 63.0, respectively); 43 male, 69 Caucasian. On the univariate analysis, there was no difference in distribution between the 2 arms for age, gender, race and ethnicity. The median PFS was 5.6 in Arm A compared to 6.7 months in Arm B (one-sided log-rank, p = 0.322). At 9 months, the progression free rates were 25.1% v. 35% for Arms A and B, respectively. The mFOLFIRINOX/ramucirumab combination was well tolerated. Patients in Arm A reported a slightly higher number of adverse events (AEs) encounters, most commonly diarrhea (29 vs 28), fatigue (25 v. 25), vomiting (24 v. 14), weight loss (23 v. 17), and abdominal pain (20 v. 15). Arm A had more SAEs than Arm B (43 v. 25), with sepsis most commonly reported in both arms (3 in each), vomiting (3 v. 2), diarrhea (3 v.1) and duodenal obstruction (3 v. 0). Arm B had a slightly higher response rate (22.58%) compared to Arm A (17.65%) that was not statistically significant. The median OS in Arm A was 10.3 compared to 9.7 months for Arm B (one-sided log-rank, p = 0.094). Conclusions: In this randomized phase 2 study, the addition of ramucirumab to mFOLFIRINOX did not improve PFS, response rate, or OS as initial therapy for metastatic pancreatic cancer. FOLFIRINOX/Ramucirumab combination was well tolerated in the treatment of PCA. Clinical trial information: NCT02581215.
Abstract 18198: Long Term Results of a Novel Approach for the Inhibition of Plaque Neovascularization. First In Man Application of Bevacizumab Eluting Stent
Authors: Konstantinos Toutouzas, Elli Stefanadi, John Karampelas, Andreas Synetos, Eleftherios Tsiamis, Dimitrios Tousoulis, Nicholas Kipishidze, Christodoulos Stefanadis
Journal: Circulation (2010)

Background: Bevacizumab is a monoclonal antibody specific for vascular endothelial growth factor, the most important mediator of neovascularization. Neovascularization plays an important role in th...
Effect of prenatal particulate matter exposure on atopic dermatitis in preschool children modified by cord blood vitamin D: COCOA study
Authors: Song-I. Yang, Hyo-Bin Kim, So-Yeon Lee, Hyun-ju Cho, Bom Kim, Hyeok Kwon, Jisun Yoon, Sungsu Jung, Hyeon-Jong Yang, Hwan-Cheol Kim, Kangmo Ahn, Kyung Won Kim, Youn Ho Sheen, Dong In Suh, Soo-Jong Hong
Journal: Journal of Allergy and Clinical Immunology (2019)
FGM: Mother is first person in UK to be convicted of female genital mutilation
Authors: Clare Dyer
Journal: BMJ (2019)

A mother whose daughter underwent female genital mutilation at the age of 3 has become the first person in the UK to be convicted of the practice.

The 37 year old woman from Uganda was found guilty after a trial at the Old Bailey in London. Her Ghanaian partner, the girl’s father, was acquitted by the jury. None of the parties can be named for legal reasons.

Remanding the woman for sentencing on 8 March, Mrs Justice Whipple warned her that she faced a lengthy jail term. Female genital mutilation carries a maximum prison sentence of 14 years. …
TCT-724 Efficacy of percutaneous left atrial appendage closure to prevent thromboembolic events in atrial fibrillation patients with high stroke and bleeding risk
Authors: Julia Seeger, Carlo Bothner, Birgid Gonska, Tillman Dahme, Dominik Scharnbeck, Sinisa Marcovic, Wolfgang Rottbauer, Jochen Wöhrle
Journal: Journal of the American College of Cardiology (2015)
The Amount of Apoptosis Predicts Outcome in Ibrutinib-Treated Chronic Lymphocytic Leukemia (CLL)
Authors: Giovanni Del Poeta, Massimiliano Postorino, Federico Pozzo, Maria Ilaria Del Principe, Enrico Santinelli, Riccardo Bomben, Annalisa Biagi, Francesco Buccisano, Francesca Maria Rossi, Adriano Venditti, Paolo de Fabritiis, Maria Cantonetti, Sergio Amadori, Valter Gattei, William Arcese
Journal: Blood (2018)
Abstract A060: Repression of microRNA-338/421 by EZH2 represents a novel mechanism for SPINK1-positive prostate cancers
Authors: Vipul Bhatia, Anjali Yadav, Ritika Tiwari, Shivansh Nigam, Apul Goel, Bushra Ateeq
Journal: Cancer Research (2018)

Abstract Prostate cancer (PCa) is a clinically heterogeneous disease marked by variability in patient prognosis. The intratumoral and interpatient heterogeneity formed the basis of molecular stratification of the disease. Overexpression of Serine Peptidase Inhibitor, Kazal type-1 (SPINK1), was found to be the second most recurrent (~10-15%) PCa subtype, after highly recurrent (~50%) androgen-driven TMPRSS2-ERG genetic rearrangement. Unlike amplification of ERBB2 in breast cancer, SPINK1 overexpression has not been associated with gene amplification or rearrangement. Nonetheless, molecular mechanism underlying its upregulation in cancer is poorly understood and remains a matter of conjecture. Using in silico microRNA prediction tools, we shortlisted three miRNAs, of which miR-338-5p and miR-421 revealed an inverse correlation with SPINK1 in The Cancer Genome Atlas (TCGA) prostate adenocarcinoma RNA-Seq dataset (n=106), which was validated in our PCa specimens (n=20). Here, we showed that miR-338-5p and miR-421 post-transcriptionally regulate SPINK1 by binding to its 3′ UTR. We established that miR-338-5p and miR-421 mediate several cellular responses against SPINK1-positive cancer by inducing S-phase cell-cycle arrest, inhibiting epithelial-to-mesenchymal transition (EMT), cancer stemness, and drug resistance. Moreover, ectopic expression of miR-338-5p and miR-421 abrogates SPINK1-mediated oncogenesis, tumor growth, and distant metastases in murine xenograft model. Further, mechanistically we demonstrate that Polycomb group protein enhancer of zeste homolog 2 (EZH2) mediates epigenetic silencing by establishing histone H3K27me3 repressive marks and DNA methylation, 5’ methyl cytosine (5mC) marks on the promoters of miR-338-5p and miR-421 in SPINK1-positive subtype. Thus, restoring miR-338-5p and miR-421 expression using either epigenetic drugs or synthetic mimics could abrogate SPINK1-mediated oncogenesis by targeting multiple oncogenic pathways and eliciting anticancer pleiotropic effects. Taken together, the present study for the first time unravels the molecular mechanism underlying SPINK1 overexpression and thereby opens up new avenues for the use of miR-338-5p and miR-421 replacement therapy for the treatment of SPINK1-positive malignancies. Citation Format: Vipul Bhatia, Anjali Yadav, Ritika Tiwari, Shivansh Nigam, Apul Goel, Bushra Ateeq. Repression of microRNA-338/421 by EZH2 represents a novel mechanism for SPINK1-positive prostate cancers [abstract]. In: Proceedings of the AACR Special Conference: Prostate Cancer: Advances in Basic, Translational, and Clinical Research; 2017 Dec 2-5; Orlando, Florida. Philadelphia (PA): AACR; Cancer Res 2018;78(16 Suppl):Abstract nr A060.
Selective IgA deficiency in humans is associated with reduced gut microbial diversity
Authors: Silje Fjellgård Jørgensen, Kristian Holm, Magnhild Eide Macpherson, Christopher Storm-Larsen, Martin Kummen, Børre Fevang, Pål Aukrust, Johannes Roksund Hov
Journal: Journal of Allergy and Clinical Immunology (2019)
Descending Marr's levels: Standard observers are no panacea
Authors: Carlos Zednik, Frank Jäkel
Journal: Behavioral and Brain Sciences (2018)

Abstract According to Marr, explanations of perceptual behavior should address multiple levels of analysis. Rahnev &amp; Denison (R&amp;D) are perhaps overly dismissive of optimality considerations at the computational level. Also, an exclusive reliance on standard observer models may cause neglect of many other plausible hypotheses at the algorithmic level. Therefore, as far as explanation goes, standard observer modeling is no panacea.
Temporal trends and disease characteristics associated with total neoadjuvant therapy (TNT) usage.
Authors: Laila Babar, Veli Bakalov, Stephen Abel, Gene Grant Finley, Moses S. Raj, Dulabh K. Monga, Alexander V. Kirichenko, Rodney E Wegner
Journal: Journal of Clinical Oncology (2019)

642 Background: Neoadjuvant chemoradiotherapy (nCRT) followed by resection and postoperative multi-agent chemotherapy (maChT) is the standard of care for locally advanced rectal cancer (LARC). Using this approach, maChT administration is delayed several months, leading to concern for high rates of distant failure. To reduce the rate of systemic failure, a novel treatment approach known as total neoadjuvant therapy (TNT) has been increasingly employed, in which patients receive both maChT and nCRT prior to resection. We utilized the National Cancer Database (NCDB) to examine temporal trends in TNT usage, as well, as any potential effect on survival. Methods: We queried the NCDB for patients diagnosed with LARC (Stage II-III) from 2004–2015 treated with nCRT or TNT. TNT was defined as maChT initiated ≥ 90 days prior to the start of nCRT. Overall survival (OS) was calculated from the date of diagnosis to the date of last contact or death using Kaplan Meier curves to present the cumulative probability of survival, with log-rank statistics used to assess statistical significance between groups. Multivariable cox regression was used to identify predictors of survival and propensity score analysis was used to account for indication bias. Results: We identified 9,066 eligible patients, with 8,812 and 254 patients receiving nCRT and TNT, respectively. Nodal involvement and Stage III disease were predictive of TNT use, as well as, treatment in in more recent year. TNT and nCRT had similar 5-year survival, 76% and 78%, respectively. MVA identified age &gt; 58, increased income, urban location, academic treatment facility, and lower co-morbidity score as predictors of worse OS. Multivariable analysis with propensity score demonstrated increased age, higher comorbidity score, higher grade, African American race, and gender as predictive of worse OS. Conclusions: Our data demonstrates a trend toward increasing TNT use, particularly in patients with greater nodal involvement or clinical stage. Despite worse disease characteristics, patients treated with TNT had similar survival to those receiving standard nCRT. Randomized trials are underway to further define the clinical benefit of TNT.
Cytotoxic CD4+ Cells in Chronic Lymphocytic Leukaemia: An Extended Immunophenotypic Analysis Examining Their Association with Cytomegalovirus Serostatus and Similarities with Cytotoxic CD8+ Cells
Authors: Maria A V Marzolini, Ayse Akarca, Karen Teng, Teresa Marafioti, Satyen H Gohil, Amit C Nathwani, Evan Newell, Sergio A Quezada, Karl S Peggs
Journal: Blood (2018)
Risk score and prognosis modeling based on mRNA expressivity in the tumor microenvironment of GI cancers.
Authors: Sunyoung S. Lee, Jessica Jerez, Ahmed Elkhanany, Fateeha Farrukh, Andrew Baird, Stuart Baird, Jillian Dolan
Journal: Journal of Clinical Oncology (2019)

608 Background: Stromal elements in the tumor microenvironment (TME) impact prognosis and response to therapy. Advances in mRNA-seq improved understanding of gene expressivity, but few models exist to model prognosis in association with mRNA expression. Methods: Clinical data and mRNA-seq of 1,715 patients (pts) – pancreatic adenocarcinoma (PAAD), colorectal adenocarcinoma (CRC), hepatocellular carcinoma (HCC), gastric adenocarcinoma (GAAD), esophageal adenocarcinoma (EsoAd), and esophageal squamous cell carcinoma (EsoSCC) – were obtained from TCGA. The expressivity of 191 genes enriched in cellular and structural components of the TME and clinical data were analyzed using machine learning, multivariable COX model, and Kaplan-Meier (KM) analysis to model risk score (RS) to predict prognosis. Results: Genes associated with good and poor prognosis were identified via machine learning and statistic methods. Higher RS represents worse prognosis with max RS = 1 (Table). In all 6 cancers, high P/G (the expression ratio of genes associated with poor to good prognosis) and old age are related to worse survival except EsoAd with younger pts having worse prognosis. The location of tumors in CRC and sex in HCC impact RS. When pts are grouped into 3 pt groups in each cancer, KM curves in pts with low, intermediate, and high RS are statistically different (p &lt; 0.0001) with high hazard ratio (HR &gt; 2). Conclusions: Analysis of large data was assisted by machine learning and statistics, identifying genes associated with survival and creating RS as a tool to predict prognosis. This provides valuable information about prognosis for pts encountered in the clinic when genomic profiles are given. Computational modeling to predict response to chemotherapy and immunotherapy is underway. [Table: see text]
Abstract 16715: Projected Costs of Informal Caregiving for Cardiovascular Disease: 2015 - 2035
Authors: Olga Khavjou, Sandra B Dunbar, Laurie Whitsel, Sue Nelson
Journal: Circulation (2017)

Introduction: In a recent report, AHA estimated that medical and indirect costs of CVD are expected to grow from $555 billion in 2015 to $1.1 trillion in 2035. Although significant, this estimate d...